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Focal adhesion kinase-related non-kinase ameliorates liver fibrosis by inhibiting aerobic glycolysis via the FAK/Ras/c-myc/ENO1 pathway 被引量:5
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作者 Tao Huang Yuan-Qing-Xiao Li +7 位作者 Ming-Yu Zhou Rui-Han Hu Gao-Liang Zou Jian-Chao Li Shu Feng Yong-Mei Liu Chang-Qin Xin Xue-Ke Zhao 《World Journal of Gastroenterology》 SCIE CAS 2022年第1期123-139,共17页
BACKGROUND Hepatic stellate cell(HSC)hyperactivation is a central link in liver fibrosis development.HSCs perform aerobic glycolysis to provide energy for their activation.Focal adhesion kinase(FAK)promotes aerobic gl... BACKGROUND Hepatic stellate cell(HSC)hyperactivation is a central link in liver fibrosis development.HSCs perform aerobic glycolysis to provide energy for their activation.Focal adhesion kinase(FAK)promotes aerobic glycolysis in cancer cells or fibroblasts,while FAK-related non-kinase(FRNK)inhibits FAK phosphorylation and biological functions.AIM To elucidate the effect of FRNK on liver fibrosis at the level of aerobic glycolytic metabolism in HSCs.METHODS Mouse liver fibrosis models were established by administering CCl4,and the effect of FRNK on the degree of liver fibrosis in the model was evaluated.Transforming growth factor-β1 was used to activate LX-2 cells.Tyrosine phosphorylation at position 397(pY397-FAK)was detected to identify activated FAK,and the expression of the glycolysis-related proteins monocarboxylate transporter 1(MCT-1)and enolase1(ENO1)was assessed.Bioinformatics analysis was performed to predict putative binding sites for c-myc in the ENO1 promoter region,which were validated with chromatin immunoprecipitation(ChIP)and dual luciferase reporter assays.RESULTS The pY397-FAK level was increased in human fibrotic liver tissue.FRNK knockout promoted liver fibrosis in mouse models.It also increased the activation,migration,proliferation and aerobic glycolysis of primary hepatic stellate cells(pHSCs)but inhibited pHSC apoptosis.Nevertheless,opposite trends for these phenomena were observed after exogenous FRNK treatment in LX-2 cells.Mechanistically,the FAK/Ras/c-myc/ENO1 pathway promoted aerobic glycolysis,which was inhibited by exogenous FRNK.CONCLUSION FRNK inhibits aerobic glycolysis in HSCs by inhibiting the FAK/Ras/c-myc/ENO1 pathway,thereby improving liver fibrosis.FRNK might be a potential target for liver fibrosis treatment. 展开更多
关键词 Liver fibrosis Hepatic stellate cells focal adhesion kinase focal adhesion kinase-related non-kinase Aerobic glycolysis Enolase1
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Progress in researches about focal adhesion kinase in gastrointestinal tract 被引量:8
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作者 Hui Fang Hao Yoshio Naomoto +9 位作者 Xiao-Hong Bao Nobuyuki Watanabe Kazufumi Sakurama Kazuhiro Noma Yasuko Tomono Takuya Fukazawa Yasuhiro Shirakawa Tomoki Yamatsuji Junji Matsuoka Munenori Takaoka 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第47期5916-5923,共8页
Focal adhesion kinase(FAK)is a 125-kDa non-receptor protein tyrosine.Growth factors or the clustering of integrins facilitate the rapid phosphorylation of FAK at Tyr-397 and this in turn recruits Src-family protein ty... Focal adhesion kinase(FAK)is a 125-kDa non-receptor protein tyrosine.Growth factors or the clustering of integrins facilitate the rapid phosphorylation of FAK at Tyr-397 and this in turn recruits Src-family protein tyrosine kinases,resulting in the phosphorylation of Tyr-576 and Tyr-577 in the FAK activation loop and full catalytic FAK activation.FAK plays a critical role in the biological processes of normal and cancer cells including the gastrointestinal tract.FAK also plays an important role in the restitution,cell survival and apoptosis and carcinogenesis of the gastrointestinal tract.FAK is over-expressed in cancer cells and its over-expression and elevated activities are associated with motility and invasion of cancer cells.FAK has been proposed as a potential target in cancer therapy.Small molecule inhibitors effectively inhibit the kinase activity of FAK and show a potent inhibitory effect for the proliferation and migration of tumor cells,indicating a high potential for application in cancer therapy. 展开更多
关键词 focal adhesion kinase RESTITUTION Survival and apoptosis Cancer INHIBITOR
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Focal adhesion kinase and Src phosphorylations in HGF-induced proliferation and invasion of human cholangiocarcinoma cell line, HuCCA-1 被引量:5
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作者 Urai Pongchairerk Jun-Lin Guan Vijittra Leardkamolkarn 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第37期5845-5852,共8页
AIM: To study the role of focal adhesion kinase (FAK) and its association with Src in hepatocyte growth factor (HGF)-induced cell signaling in cholangiocarcinoma progression.METHODS: Previously isolated HuCCA-1 cells ... AIM: To study the role of focal adhesion kinase (FAK) and its association with Src in hepatocyte growth factor (HGF)-induced cell signaling in cholangiocarcinoma progression.METHODS: Previously isolated HuCCA-1 cells were re-characterized by immunofluorescent staining and reverse transcriptase-polymerase chain reaction assay for the expression of cytokeratin 19, HGF and c-Met mRNA. Cultured HuCCA-1 cells were treated with HGF and determined for cell proliferation and invasion effects by MTT and invasion assays. Western blotting, immunoprecipitation, and co-immunoprecipitation were also performed to study the phosphorylation and interaction of FAK and Src. A novel Src inhibitor (AZM555130) was applied in cultures to investigate the effects on FAK phosphorylation inhibition and on cell proliferation and invasion.RESULTS: HGF enhanced HuCCA-1 cell proliferation and invasion by mediating FAK and Src phosphorylations.FAK-Src interaction occurred in a time-dependent manner that Src was proved to be an upstream signaling molecule to FAK. The inhibitor to Src decreased FAK phosphorylation level in correlation with the reduction of cell proliferation and invasion.CONCLUSION: FAK plays a significant role in signaling pathway of HGF-responsive cell line derived from cholangiocarcinoma. Autophosphorylated Src, induced by HGF, mediates Src kinase activation, which subsequently phosphorylates its substrate, FAK, and signals to cell proliferation and invasion. 展开更多
关键词 Human cholangiocarcinoma Hepatocyte growth factor C-MET focal adhesion kinase SRC
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Inhibition of focal adhesion kinase enhances antitumor response of radiation therapy in pancreatic cancer through CD8+ T cells 被引量:4
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作者 Arsen Osipov Alex B.Blair +14 位作者 Juliane Liberto Jianxin Wang Keyu Li Brian Herbst Yao Xu Shiqi Li Nan Niu Rufiaat Rashid Ding Ding Yanan Liu Zaiqi Wang Christopher L.Wolfgang Richard A.Burkhart Daniel Laheru Lei Zheng 《Cancer Biology & Medicine》 SCIE CAS CSCD 2021年第1期206-214,共9页
Objective:Pancreatic ductal adenocarcinoma(PDAC)is a deadly malignancy,due in large part to its resistance to conventional therapies,including radiotherapy(RT).Despite RT exerting a modest antitumor response,it has al... Objective:Pancreatic ductal adenocarcinoma(PDAC)is a deadly malignancy,due in large part to its resistance to conventional therapies,including radiotherapy(RT).Despite RT exerting a modest antitumor response,it has also been shown to promote an immunosuppressive tumor microenvironment.Previous studies demonstrated that focal adhesion kinase inhibitors(FAKi)in clinical development inhibit the infiltration of suppressive myeloid cells and T regulatory(T regs)cells,and subsequently enhance effector T cell infiltration.FAK inhibitors in clinical development have not been investigated in combination with RT in preclinical murine models or clinical studies.Thus,we investigated the impact of FAK inhibition on RT,its potential as an RT sensitizer and immunomodulator in a murine model of PDAC.Methods:We used a syngeneic orthotopic murine model to study the effect of FAKi on hypofractionated RT.Results:In this study we showed that IN10018,a small molecular FAKi,enhanced antitumor response to RT.Antitumor activity of the combination of FAKi and RT is T cell dependent.FAKi in combination with RT enhanced CD8+T cell infiltration significantly in comparison to the radiation or FAKi treatment alone(P<0.05).FAKi in combination with radiation inhibited the infiltration of granulocytes but enhanced the infiltration of macrophages and T regs in comparison with the radiation or FAKi treatment alone(P<0.01).Conclusions:These results support the clinical development of FAKi as a radiosensitizer for PDAC and combining FAKi with RT to prime the tumor microenvironment of PDAC for immunotherapy. 展开更多
关键词 focal adhesion protein-tyrosine kinases RADIOTHERAPY pancreatic neoplasms IMMUNOMODULATION
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Effect of focal adhesion kinase on cytoskeletal arrangement of HepG2 cells induced by hypoxia 被引量:4
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作者 Wei Yan Yu Fu Jiazhi Liao Limin Xia Min Luo Qian Zhu Dean Tian 《The Chinese-German Journal of Clinical Oncology》 CAS 2009年第3期129-133,共5页
Objective: To study focal adhesion kinase (FAK) expression in hypoxic HepG2 cells and the effect of FAK siRNA on cytoskeletal arrangement of HepG2 cells induced by hypoxia. Methods: HepG2 cells were cultured in 21... Objective: To study focal adhesion kinase (FAK) expression in hypoxic HepG2 cells and the effect of FAK siRNA on cytoskeletal arrangement of HepG2 cells induced by hypoxia. Methods: HepG2 cells were cultured in 21% O2 and 1% O2. Morphological changes were observed after hypoxia treatment. Western blot was used to measure FAK expression. The siRNA expression vector pshRNA-FAK targeting the mRNA of FAK and vector pGensil-2 (as a control) were constructed, and then transfected into HepG2 cells. Western blot was used to detect FAK. The cytoskeletal arrangement of HepG2 cells transfected with pshRNA-FAK induced by hypoxia was analyzed by phalloidin. The migratory ability of HepG2 cells transfected with pshRNA-FAK induced by hypoxia was analyzed by cell migration assay. Results: Hypoxia-treated cells displayed a more elongated shape with a large degree of cell detachment. FAK expression increased in hypoxic HepG2 cells. FAK protein level was decreased by 75.64% ± 3.12% (P 〈 0.01) after the pshRNA-FAK transfection. Hypoxia induced cytoskeletal arrangement of HepG2 cells. However, cytoskeletal arrangement of HepG2 cells transfected with pshRNA-FAK induced by hypoxia was inhibited in 1% O2. As cell migration assay showed, the migrating number of HepG cells transfected with pshRNA-FAK was significantly lower than that of control (P 〈 0.05). Conclusion: The expression of FAK in hypoxic HCC might have a close relationship to the cytoskeletal arrangement of HepG2 cells induced by hypoxia. Up-regulation of FAK expression may be one of mechanisms of cytoskeletal arrangement and invasion of hepatocellular carcinoma induced by hypoxia. 展开更多
关键词 carcinoma hepatocellular HYPOXIA RNA interference focal adhesion kinase (FAK) cytoskeletal arrangement
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The Overexpressed FAK (Focal Adhesion Kinase) in Higher Grade Human Urothelial Tumors 被引量:1
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作者 Baz Ahsene Ousmaal Mohamed E +6 位作者 Fadell Mammeri Saadia Zineddine-Charef Amir Frederic Boudard Frederic Hollande Belal Tahar Jean Giaimis 《Journal of Life Sciences》 2013年第1期1-7,共7页
Malignant transformation of normal cells involves important structural and functional changes, particularly in cell adhesion. In this study, we wanted to assess whether changes in the expression of FAK, a tyrosine kin... Malignant transformation of normal cells involves important structural and functional changes, particularly in cell adhesion. In this study, we wanted to assess whether changes in the expression of FAK, a tyrosine kinase, which is recruited to focal adhesions and plays a key role in cell migration, proliferation and survival, could reflect the invasive capacity of bladder carcinomas. The aim of this study was to evaluate the FAK expression in cancer ceils as an important prognostic factor of the evolution of bladder carcinomas. Tumor and paired peritumoral biopsies were obtained during transurethral endoscopic resection or cystectomy of bladder tumors in 280 patients at the Urology Unit of the Mustapha Hospital of Algiers and the Hospital of Tizi-Ouzou (Algeria). The authors studied FAK expression in samples from bladder carcinomas at different stages of malignant transformation by western blot analysis using a specific anti-FAK antibody. Western blot is one of the most common laboratory techniques; it is used to detect the presence of a specific protein in a complex mixture extracted from cells. A weak increase in FAK expression was observed in tumors of grade 1 and 2 (1.65; 2.99) as compared to healthy tissues; it became particularly important in grade 3 tumors; the authors show that FAK levels significantly increased gradually according to the tumor stage. 展开更多
关键词 BLADDER CANCER focal adhesion kinase retrodifferentiation.
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Stability of focal adhesion enhanced by its inner force fluctuation
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作者 毛志秀 陈笑风 陈彬 《Chinese Physics B》 SCIE EI CAS CSCD 2015年第8期632-638,共7页
Cells actively sense and respond to mechanical signals from the extracellular matrix through focal adhesions. By representing a single focal adhesion as a cluster of slip bonds, it has been demonstrated that the clust... Cells actively sense and respond to mechanical signals from the extracellular matrix through focal adhesions. By representing a single focal adhesion as a cluster of slip bonds, it has been demonstrated that the cluster often became unstable under fluctuated forces. However, an unusual case was also reported, where the stability of the cluster might be substantially enhanced by a fluctuated force with a relatively low fluctuation frequency and high fluctuation amplitude.Such an observation cannot be explained by the conventional fracture theory of fatigue. Here, we intensively investigate this intriguing observation by carrying out systematic parametric studies. Our intensive simulation results indicate that stability enhancement of this kind is in fact quite robust, which can be affected by the stochastic features of a single bond and the profile of the fluctuated forces such as the average value of bond force. We then suggest that the fluctuation of traction force within a focal adhesion might enhance its stability in a certain way. 展开更多
关键词 focal adhesion slip bonds STABILITY fluctuated forces
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Rbfox1 controls alternative splicing of focal adhesion genes in cardiac muscle cells
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作者 Peter Zorn Jaime Calvo Sánchez +4 位作者 Tala Alakhras Barbara Schreier Michael Gekle Stefan Hüttelmaier Marcel Köhn 《Journal of Molecular Cell Biology》 SCIE CAS CSCD 2024年第1期54-65,共12页
Alternative splicing is one of the major cellular processes that determine the tissue-specific expression of protein variants.However,it remains challenging to identify physiologically relevant and tissue-selective pr... Alternative splicing is one of the major cellular processes that determine the tissue-specific expression of protein variants.However,it remains challenging to identify physiologically relevant and tissue-selective proteins that are generated by alternative splicing.Hence,we investigated the target spectrum of the splicing factor Rbfox1 in the cardiac muscle context in more detail.By using a combination of in silico target prediction and in-cell validation,we identified several focal adhesion proteins as alternative splicing targets of Rbfox1.We focused on the alternative splicing patterns of vinculin(metavinculin isoform)and paxillin(extended paxillin isoform)and identified both as potential Rbfox1 targets.Minigene analyses suggested that both isoforms are promoted by Rbfox1 due to binding in the introns.Focal adhesions play an important role in the cardiac muscle context,since they mainly influence cell shape,cytoskeletal organization,and cell–matrix association.Our data confirmed that depletion of Rbfox1 changed cardiomyoblast morphology,cytoskeletal organization,and multinuclearity after differentiation,which might be due to changes in alternative splicing of focal adhesion proteins.Hence,our results indicate that Rbfox1 promotes alternative splicing of focal adhesion genes in cardiac muscle cells,which might contribute to heart disease progression,where downregulation of Rbfox1 is frequently observed. 展开更多
关键词 Rbfox1 alternative splicing focal adhesion cardiac muscle cells
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Roles of focal adhesion proteins in skeleton and diseases 被引量:3
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作者 Sheng Chen Tailin He +5 位作者 Yiming Zhong Mingjue Chen Qing Yao Di Chen Zengwu Shao Guozhi Xiao 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2023年第3期998-1013,共16页
The skeletal system,which contains bones,joints,tendons,ligaments and other elements,plays a wide variety of roles in body shaping,support and movement,protection of internal organs,production of blood cells and regul... The skeletal system,which contains bones,joints,tendons,ligaments and other elements,plays a wide variety of roles in body shaping,support and movement,protection of internal organs,production of blood cells and regulation of calcium and phosphate metabolism.The prevalence of skeletal diseases and disorders,such as osteoporosis and bone fracture,osteoarthritis,rheumatoid arthritis,and intervertebral disc degeneration,increases with age,causing pain and loss of mobility and creating a huge social and economic burden globally.Focal adhesions(FAs)are macromolecular assemblies that are composed of the extracellular matrix(ECM),integrins,intracellular cytoskeleton and other proteins,including kindlin,talin,vinculin,paxillin,pinch,Src,focal adhesion kinase(FAK)and integrin-linked protein kinase(ILK)and other proteins.FA acts as a mechanical linkage connecting the ECM and cytoskeleton and plays a key role in mediating cell–environment communications and modulates important processes,such as cell attachment,spreading,migration,differentiation and mechanotransduction,in different cells in skeletal system by impacting distinct outside-in and inside-out signaling pathways.This review aims to integrate the up-to-date knowledge of the roles of FA proteins in the health and disease of skeletal system and focuses on the specific molecular mechanisms and underlying therapeutic targets for skeletal diseases. 展开更多
关键词 focal adhesion SKELETON MECHANOTRANSDUCTION Signal transduction INTEGRIN Cartilage Intervertebral disc Skeletal diseases
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Focal adhesion kinase signaling is necessary for the hydrogen sulfide-enhanced proliferation,migration,and invasion of HTR8/SVneo human trophoblasts
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作者 Xian-Li Wang Jing Tang 《Reproductive and Developmental Medicine》 CAS CSCD 2023年第2期75-82,共8页
Objective:Hydrogen sulfide(H_(2)S)has been elucidated that it promotes migration and invasion in human placenta trophoblasts.However,the signaling pathway underlying H_(2)S-based regulation of trophoblasts remains unk... Objective:Hydrogen sulfide(H_(2)S)has been elucidated that it promotes migration and invasion in human placenta trophoblasts.However,the signaling pathway underlying H_(2)S-based regulation of trophoblasts remains unknown.Hence,we investigated the potential effect of sodium hydrosulfide(NaHS),an exogenous H_(2)S donor,on extravillous trophoblasts.Methods:The Cell Counting Kit-8 was used to detect the proliferative activity of trophoblasts and to screen the optimal concentration of NaHS.The migration and invasion of HTR8/SVneo cells were measured by Transwell assays.Gene expression was determined by quantitative real-time PCR analysis.Protein expression was determined by western blot.Results:We found that NaHS could promote the proliferation,migration,and invasion of HTR8/SVneo cells.The phosphorylation of focal adhesion kinase(FAK),Src,and extracellular signal-regulated kinase(ERK)were activated by NaHS.Moreover,NaHS also upregulated the expression of matrix metalloproteinase-2(MMP-2)and MMP-9,downregulated the expression of E-cadherin in HTR8/SVneo cells.The application of NaHS could increase the expression of cystathionine-β-synthase.Conclusion:Both FAK-Src signaling and the upstream signaling cascade of ERK activation play a significant important role in NaHS-induced proliferation,migration,and invasion via upregulating activity of MMP-2,MMP-9,and downregulating E-cadherin in HTR8/SVneo cells.These novel findings may provide a strong foundation for the clinical application of H_(2)S donor drugs. 展开更多
关键词 Hydrogen sulfide TROPHOBLAST PROLIFERATION MIGRATION INVASION focal adhesion kinase signaling
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Ihog proteins contribute to integrin-mediated focal adhesions
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作者 Yun Qi Han Liu +3 位作者 Kang Zhang Yihui Wu Chenghao Shen Xinhua Lin 《Science China(Life Sciences)》 SCIE CAS CSCD 2023年第2期366-375,共10页
Integrin expression forms focal adhesions, but how this process is physiologically regulated is unclear. Ihog proteins are evolutionarily conserved, playing roles in Hedgehog signaling and serving as trans-homophilic ... Integrin expression forms focal adhesions, but how this process is physiologically regulated is unclear. Ihog proteins are evolutionarily conserved, playing roles in Hedgehog signaling and serving as trans-homophilic adhesion molecules to mediate cell-cell interactions. Whether these proteins are also engaged in other cell adhesion processes remains unknown. Here, we report that Drosophila Ihog proteins function in the integrin-mediated adhesions. Removal of Ihog proteins causes blister and spheroidal muscle in wings and embryos, respectively. We demonstrate that Ihog proteins interact with integrin via the extracellular portion and that their removal perturbs integrin distribution. Finally, we show that Boc, a mammalian Ihog protein,rescues the embryonic defects caused by removing its Drosophila homologs. We thus propose that Ihog proteins contribute to integrin-mediated focal adhesions. 展开更多
关键词 INTEGRIN focal adhesion Ihog/Boi DROSOPHILA
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Ion elemental-optimized layered double hydroxide nanoparticles promote chondrogenic differentiation and intervertebral disc regeneration of mesenchymal stem cells through focal adhesion signaling pathway
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作者 Zhaojie Wang Huiyi Yang +5 位作者 Xu Xu Hongxing Hu Yuxin Bai Jian Hai Liming Cheng Rongrong Zhu 《Bioactive Materials》 SCIE CSCD 2023年第4期75-90,共16页
Chronic low back pain and dyskinesia caused by intervertebral disc degeneration(IDD)are seriously aggravated and become more prevalent with age.Current clinical treatments do not restore the biological structure and i... Chronic low back pain and dyskinesia caused by intervertebral disc degeneration(IDD)are seriously aggravated and become more prevalent with age.Current clinical treatments do not restore the biological structure and inherent function of the disc.The emergence of tissue engineering and regenerative medicine has provided new insights into the treatment of IDD.We synthesized biocompatible layered double hydroxide(LDH)nanoparticles and optimized their ion elemental compositions to promote chondrogenic differentiation of human umbilical cord mesenchymal stem cells(hUC-MSCs).The chondrogenic differentiation of LDH-treated MSCs was validated using Alcian blue staining,qPCR,and immunofluorescence analyses.LDH-pretreated hUC-MSCs were differentiated prior to transplantation into the degenerative site of a needle puncture IDD rat model.Repair and regeneration evaluated using X-ray,magnetic resonance imaging,and tissue immunostaining 4-12 weeks after transplantation showed recovery of the disc space height and integrated tissue structure.Transcriptome sequencing revealed significant regulatory roles of the extracellular matrix(ECM)and integrin receptors of focal adhesion signaling pathway in enhancing chondrogenic differentiation and thus prompting tissue regeneration.The construction of ion-specific LDH nanomaterials for in situ intervertebral disc regeneration through the focal adhesion signaling pathway provides theoretical basis for clinical transformation in IDD treatment. 展开更多
关键词 Mesenchymal stem cells Layered double hydroxide Chondrogenic differentiation Intervertebral disc degeneration focal adhesion signaling pathway
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Activated focal adhesion kinase involved in adhesion and migration of vascular smooth muscle cells stimulated by fibronectin
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作者 尹航 汪丽蕙 +3 位作者 霍勇 彭旭 夏春芳 唐朝枢 《Chinese Medical Journal》 SCIE CAS CSCD 2002年第4期494-497,共4页
OBJECTIVE: To study the effects of focal adhesion kinase (FAK) phosphorylation on smooth muscle cells (SMCs) adhesion and migration stimulated by fibronectin. METHODS: Adhesion and migration of cultured SMCs were stim... OBJECTIVE: To study the effects of focal adhesion kinase (FAK) phosphorylation on smooth muscle cells (SMCs) adhesion and migration stimulated by fibronectin. METHODS: Adhesion and migration of cultured SMCs were stimulated by different concentrations of fibronectin (FN), FAK and its phosphorylation were detected by immunoprecipitation and Western blot. FAK antisense oligodeoxynucleotides (ODNs) were transfected into SMCs by cationic lipid to investigate its modulatory effects on tyrosine phosphorylation. SMCs adhesion and migration were also measured by morphological enumeration and modified Boyden Chambers, respectively. RESULTS: FAK were expressed when SMCs adhesion and migration were successfully simulated by different concentrations of FN. FAK phosphorylation were detected only at 20 microg/ml FN or more. FAK antisense ODNs were transfected efficiently by cationic lipid and FAK phosphorylation was inhibited substantially. The SMCs migration rate in the 5 - 60 microg/ml FN groups was reduced by 17.89% - 27.67%. Cell migration stimulated by FN at 10, 20, 40 and 60 microg/ml were reduced by 23.26%, 21.63%, 19.31% and 17.88%, respectively (P 展开更多
关键词 Animals Cell adhesion Cell Movement Cells Cultured DNA Antisense Dose-Response Relationship Drug Enzyme Activation FIBRONECTINS focal adhesion Kinase 1 focal adhesion Protein-Tyrosine Kinases Muscle Smooth Vascular PHOSPHORYLATION Protein-Tyrosine Kinase Rats TRANSFECTION
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Activated focal adhesion kinase involved in adhesion and migration of vas cular smooth muscle cells stimulated by fibronectin
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作者 尹航 汪丽蕙 +3 位作者 霍勇 彭旭 夏春芳 唐朝枢 《Chinese Medical Journal》 SCIE CAS CSCD 2002年第4期14-17,145-146,共6页
To study the effects of focal adhesion kinase (FAK) phosphorylation on smooth mu scle cells (SMCs) adhesion and migration stimulated by fibronectin Methods Adhesion and migration of cultured SMCs were stimulated by ... To study the effects of focal adhesion kinase (FAK) phosphorylation on smooth mu scle cells (SMCs) adhesion and migration stimulated by fibronectin Methods Adhesion and migration of cultured SMCs were stimulated by different concentrati ons of fibronectin (FN), FAK and its phosphorylation were detected by immunoprec ipitation and Western blot FAK antisense oligodeoxynucleotides (ODNs) were tra nsfected into SMCs by cationic lipid to investigate its modulatory effects on ty rosine phosphorylation SMCs adhesion and migration were also measured by morph ological enumeration and modified Boyden Chambers, respectively Results FAK were expressed when SMCs adhesion and migration were successfully simulated by different concentrations of FN FAK phosphorylation were detected only at 20 ?μg/ml FN or more FAK antisense ODNs were transfected efficiently by cationi c lipid and FAK phosphorylation was inhibited substantially The SMCs migration rate in the 5-60?μg/ml FN groups was reduced by 17 89%-27 67% Cell migrat ion stimulated by FN at 10, 20, 40 and 60?μg/ml were reduced by 23 26%, 21 6 3%, 19 31% and 17 88%, respectively ( P 【0 05) Conclusions FAK phosphorylation and FAK mediated signal transduction play important roles i n SMCs adhesion and migration stimulated by ECM The process can be inhibited e ffectively by FAK antisense ODNs 展开更多
关键词 focal adhesion kinase · vascular smooth muscle cells · antisense oligodeoxynucleotides · adhesion · migrat ion
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MicroRNA-7 regulates glioblastoma cell invasion via targeting focal adhesion kinase expression 被引量:24
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作者 WU De-gang WANG Ying-yi FAN Li-gang LUO Hui HAN Bin SUN Li-hua WANG Xie-feng ZHANG Jun-xia CAO Lei WANG Xi-rui YOU Yong-ping LIU Ning 《Chinese Medical Journal》 SCIE CAS CSCD 2011年第17期2616-2621,共6页
Background Invasion growth is the most characteristic biological phenotype of glioblastoma, but the molecular mechanism in glioma cell invasion is poorly understood. Recent data have showed that microRNA plays an esse... Background Invasion growth is the most characteristic biological phenotype of glioblastoma, but the molecular mechanism in glioma cell invasion is poorly understood. Recent data have showed that microRNA plays an essential role in tumor invasion. Our study aimed to explore the mechanism of miR-7 involved in the control of glioblastoma cell invasion. Methods Glioma cell invasion was evaluated by transwell and scratch assays after up-regulation of miR-7 using miR-7 mimics in U87 and U251 cells. Luciferase reporter assay was used to determine focal adhesion kinase (FAK) as a target of miR-7. The levels of miR-7, matrix metalloproteinases (MMP)-2 and MMP-9 mRNA were detected by PCR assay, and the levels of FAK, MMP-2, MMP-9, total and phosphorylation serine/threonine kinase (AKT), and extracellular signal-regulated kinase (ERK) 1/2 were measured by Western blotting analysis. Results Over-expression of miR-7 inhibited the invasion and migration activity of U87 and U251 cells. And up-regulation of miR-7 reduced FAK protein expression, Further, luciferase reporter assay showed that miR-7 modulated FAK expression directly by binding 3'UTR of FAK mRNA. In addition, miR-7 repressed p-ERK1/2 and p-AKT level, MMP-2 and MMP-9 expression. Finally, the inverse relationship between FAK and miR-7 expression was certificated in human glioma tissues. Conclusion To our knowledge, these data indicate for the first time that miR-7 directly regulates cell invasion by targeting FAK in glioblastoma and that miR-7 could be a potential therapeutic target for glioblastoma intervention. 展开更多
关键词 MICRORNA GLIOBLASTOMA cell invasion focal adhesion kinase
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Focal adhesion kinase antisense oligodeoxynucleotides inhibit human pulmonary artery smooth muscle cells proliferation and promote human pulmonary artery smooth muscle cells apoptosis 被引量:24
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作者 LINChun-long ZHANGZhen-xiang +2 位作者 XUYong-jian NIWang CHENShi-xin 《Chinese Medical Journal》 SCIE CAS CSCD 2005年第1期20-26,共7页
Background Pulmonary artery smooth muscle cell (PASMC) proliferation plays an important role in pulmonary vessel structural remodelling At present, the mechanisms related to proliferation of PASMCs are not clear ... Background Pulmonary artery smooth muscle cell (PASMC) proliferation plays an important role in pulmonary vessel structural remodelling At present, the mechanisms related to proliferation of PASMCs are not clear Focal adhesion kinase (FAK) is a widely expressed nonreceptor protein tyrosine kinase Recent research indicates that FAK is implicated in signalling pathways which regulate cytoskeletal organization, adhesion, migration, survival and proliferation of cells Furthermore, there are no reports about the role of FAK in human pulmonary artery smooth muscle cells (HPASMCs) We investigated whether FAK takes part in the intracellular signalling pathway involved in HPASMCs proliferation and apoptosis, by using antisense oligodeoxynucleotides (ODNs) to selectively suppress the expression of FAK protein Methods Cultured HPASMCs stimulated by fibronectin (40 μg/ml) were passively transfected with ODNs, sense FAK, mismatch sense and antisense FAK respectively Expression of FAK, Jun NH2 terminal kinase (JNK), cyclin dependent kinase 2 (CDK 2) and caspase 3 proteins were detected by immunoprecipitation and Western blots Cell cycle and cell apoptosis were analysed by flow cytometry In addition, cytoplasmic FAK expression was detected by immunocytochemical staining Results When compared with mismatch sense group, the protein expressions of FAK, JNK and CDK 2 in HPASMCs decreased in antisense FAK ODNs group and increased in sense FAK ODNs group significantly Caspase 3 expression upregulated in HPASMCs when treated with antisense ODNs and downregulated when treated with sense ODNs When compared with mismatch sense ODNs group, the proportion of cells at G 1 phase decreased significantly in sense ODNs group, while the proportion of cells at S phase increased significantly In contrast, compared with mismatch sense ODNs group, the proportion of cells at G 1 phase was increased significantly in antisense FAK ODNs group The level of cell apoptosis in antisense FAK group was higher than in the mismatch sense group and the latter was higher than sense FAK group In addition, the sense FAK ODNs group was strongly stained by immunocytochemistry, whereas the antisense FAK ODNs group was weakly stained Conclusions The results suggest that FAK relates to the proliferation of HPASMCs Antisense FAK ODNs inhibit HPASMCs proliferation and facilitate their apoptosis It is possible that FAK via JNK, CDK 2 signalling pathways enhances HPASMCs proliferation and via caspase 3 inhibits HPASMCs apoptosis 展开更多
关键词 human pulmonary artery smooth muscle cells · focal adhesion kinase · proliferation · apoptosis RESPIRATORY
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Expression, distribution and function of the focal adhesion kinase (pp125^(FAK)) during murine ectoplacental cone outgrowth in vitro 被引量:5
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作者 ZHANG Chunyu DUAN Enkui +1 位作者 CAO Yujing ZENG Guoqing 《Chinese Science Bulletin》 SCIE CAS 1998年第17期1473-1480,共8页
Mouse embryo implantation is a complex process that includes trophoblast cells derived from ectoplacental cone (EPC) adhesion to and migration through the extracellular matrix (ECM) of uterine endometrium and invasion... Mouse embryo implantation is a complex process that includes trophoblast cells derived from ectoplacental cone (EPC) adhesion to and migration through the extracellular matrix (ECM) of uterine endometrium and invasion into the decidua. At the time of implantation, fibronectin (FN) is abundant in the decidua and is distributed pericellularly around each individual stromal cell, and its receptor (integrin α-5β-1) expression on trophoblast populations is up-regulated. The focal adhesion kinase, a 125 ku protein tyrosine kinase (pp125 FAK), is tyrosine phosphorylated upon integrin engagement with its ECM ligand, and its tyrosine phosphorylation sites then serve as the binding sites which couple it with cellular proteins that contain Src SH2 or SH3 domains. Through these linkages, pp125 FAK may integrate multiple signals triggered by integrins. The model of EPC culture %in vitro% was used to study the expression, distribution and function of pp125 FAK during EPC outgrowth on FN. Results indicated that, pp125 FAK primarily expressed and distributed in cellular focal adhesions of the front edge of trophoblast outgrowth from EPC, and was localized in the peripheral region of the individual migrating trophblast cell; antibody or antisense oligodeoxynucleotide to pp125 FAK inhibited EPC attachment and outgrowth, as well as trophoblast cells spreading and migration. This experiment demonstrated that pp125 FAK as an integrin-mediated signaling molecule was involved in EPC outgrowth %in vitro%, and played an important role during trophoblast cells interaction with FN. 展开更多
关键词 FIBRONECTIN INTEGRIN focal adhesion kinase(pp125 FAK) ectoplacental cone attachment outgrowth.
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Jianpijiedu Fang improves survival of hepatocarcinoma mice by affecting phosphatase and tensin homolog, phosphoinositide 3-kinase, and focal adhesion kinase 被引量:12
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作者 Baoguo Sun Jun Meng +5 位作者 Ting Xiang Zexiong Chen Yulong Li Lisha Lu Shijun Zhang Xiaolin Chen 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2013年第4期479-485,共7页
OBJECTIVE: To investigate the effect of Jianpijiedu Fang (JPJDF) on phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), and focal adhesion kinase (FAK), and on the survival of hepatocellular carci... OBJECTIVE: To investigate the effect of Jianpijiedu Fang (JPJDF) on phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), and focal adhesion kinase (FAK), and on the survival of hepatocellular carcinoma (HCC) nude mice. METHODS: Forty male nude mice were randomly divided into 4 groups. Human HCC tissue was implanted in the livers of three groups. After 24 h, the three groups were treated respectively with JPJDF (37.5 g/kg), saline (20 mL/kg) and Tegafur (FT-207, 160 mg/kg) once a day for 10 weeks. The control group without implanting the tissue was concurrently treated with saline (20 mL/kg). The survival data and body weight of all mice were recorded, and expression levels of PTEN, PI3K and FAK in normal tissue and cancer tissue of the livers were eval-uated with immunohistochemical method. RESULTS: The cumulative survival rate of the mice in the JPJDF group was higher than those of the other groups. The rate of weight loss was the lowest in JPJDF group. The survivability and weight loss rate in FT-207 group were the poorest in all groups. The expression intensity of PTEN was higher in normal tissues than in cancer tissues, and lower in the normal tissues of HCC models than in that of mice without HCC. The PTEN expression intensity in normal tissue and cancer tissue from mice treated with FT-207 were lower than that from the mice treated with JPJDF or saline.The expression intensity of PI3K was higher in cancer tissue than in normal tissue. The PI3K expression intensity was the lowest in normal tissue and cancer tissue from mice treated with JPJDF, and the intensity from mice treated with FT-207 was the highest. In mice treated with JPJDF, the expression intensity of FAK was higher in the normal tissue and lower in the cancer tissue than those of the other treatment groups. CONCLUSION: The mechanism accounting for the prolonged survival of HCC-bearing mice treated with JPJDF might be related to the reduction in weight loss and the benign regulation of PTEN, PI3K, and FAK. 展开更多
关键词 Liver neoplasms Pten protein mouse Phosphatidylinositol 3-kinase focal adhesion protein-tyrosine kinases Jianpijiedu Fang
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F-Actin reassembly during focal adhesion impacts single cell mechanics and nanoscale membrane structure 被引量:1
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作者 ZIMMER Christopher C SHI LiFang +4 位作者 SHIH YiPing LI JieRen JIN LeeWay LO SuHao LIU GangYu 《Science China Chemistry》 SCIE EI CAS 2012年第9期1922-1930,共9页
Focal adhesions play an important role in cell spreading,migration,and overall mechanical integrity.The relationship of cell structural and mechanical properties was investigated in the context of focal adhesion proce... Focal adhesions play an important role in cell spreading,migration,and overall mechanical integrity.The relationship of cell structural and mechanical properties was investigated in the context of focal adhesion processes.Combined atomic force microscopy(AFM) and laser scanning confocal microscopy(LSCM) was utilized to measure single cell mechanics,in correlation with cellular morphology and membrane structures at a nanometer scale.Characteristic stages of focal adhesion were verified via confocal fluorescent studies,which confirmed three representative F-actin assemblies,actin dot,filaments network,and long and aligned fibrous bundles at cytoskeleton.Force-deformation profiles of living cells were measured at the single cell level,and displayed as a function of height deformation,relative height deformation and relative volume deformation.As focal adhesion progresses,single cell compression profiles indicate that both membrane and cytoskeleton stiffen,while spreading increases especially from focal complex to focal adhesion.Correspondingly,AFM imaging reveals morphological geometries of spherical cap,spreading with polygon boundaries,and elongated or polarized spreading.Membrane features are dominated by protrusions of 41-207 nm tall,short rods with 1-6 μm in length and 10.2-80.0 nm in height,and long fibrous features of 31-246 nm tall,respectively.The protrusion is attributed to local membrane folding,and the rod and fibrous features are consistent with bilayer decorating over the F-actin assemblies.Taken collectively,the reassembly of F-actin during focal adhesion formation is most likely responsible for the changes in cellular mechanics,spreading morphology,and membrane structural features. 展开更多
关键词 focal adhesion actin fibers actin assembly FIBROBLAST membrane structure single cell mechanics atomic forcemicroscopy laser scanning confocal microscopy
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Profiling the responsiveness of focal adhesions of human cardiomyocytes to extracellular dynamic nano-topography 被引量:1
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作者 Huaiyu Shi Xiangjun Wu +7 位作者 Shiyang Sun Chenyan Wang Zacharias Vangelatos Ariel Ash-Shakoor Costas P.Grigoropoulos Patrick T.Mather James H.Henderson Zhen Ma 《Bioactive Materials》 SCIE 2022年第4期367-377,共11页
Focal adhesion complexes function as the mediators of cell-extracellular matrix interactions to sense and transmit the extracellular signals.Previous studies have demonstrated that cardiomyocyte focal adhesions can be... Focal adhesion complexes function as the mediators of cell-extracellular matrix interactions to sense and transmit the extracellular signals.Previous studies have demonstrated that cardiomyocyte focal adhesions can be modulated by surface topographic features.However,the response of focal adhesions to dynamic surface topographic changes remains underexplored.To study this dynamic responsiveness of focal adhesions,we utilized a shape memory polymer-based substrate that can produce a flat-to-wrinkle surface transition triggered by an increase of temperature.Using this dynamic culture system,we analyzed three proteins(paxillin,vinculin and zyxin)from different layers of the focal adhesion complex in response to dynamic extracellular topographic change.Hence,we quantified the dynamic profile of cardiomyocyte focal adhesion in a time-dependent manner,which provides new understanding of dynamic cardiac mechanobiology. 展开更多
关键词 Stimuli-responsive biomaterials Shape memory polymer focal adhesion Costamere Dynamic mechanobiology Human induced pluripotent stem cells
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