Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expr...Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.展开更多
Background:Inhibitor of NF-κB kinase-interacting protein(IKIP)is known to promote proliferation of glioblastoma(GBM)cells,but how it affects migration and invasion by those cells is unclear.Methods:We compared levels...Background:Inhibitor of NF-κB kinase-interacting protein(IKIP)is known to promote proliferation of glioblastoma(GBM)cells,but how it affects migration and invasion by those cells is unclear.Methods:We compared levels of IKIP between glioma tissues and normal brain tissue in clinical samples and public databases.We examined the effects of IKIP overexpression and knockdown on the migration and invasion of GBM using transwell and wound healing assays,and we compared the transcriptomes under these different conditions to identify the molecular mechanisms involved.Results:Based on data from our clinical samples and from public databases,IKIP was overexpressed in GBM tumors,and its expression level correlated inversely with survival.IKIP overexpression in GBM cells inhibited migration and invasion in transwell and wound healing assays,whereas IKIP knockdown exerted the opposite effects.IKIP overexpression in GBM cells that were injected into mouse brain promoted tumor growth but inhibited tumor invasion of surrounding tissue.The effects of IKIP were associated with downregulation of THBS1 mRNA and concomitant inhibition of THBS1/FAK signaling.Conclusions:IKIP inhibits THBS1/FAK signaling to suppress migration and invasion of GBM cells.展开更多
目的:研究粘着斑激酶(focal adhesion kinase,FAK)、磷酸化粘着斑激酶(phospho-FAK,Y397)、与张力蛋白同源的第10号染色体丢失的磷酸酶基因(phosphatase and tensinhomolog deleted on chromosome,PTEN)在胃腺癌及癌旁组织中的表达及其...目的:研究粘着斑激酶(focal adhesion kinase,FAK)、磷酸化粘着斑激酶(phospho-FAK,Y397)、与张力蛋白同源的第10号染色体丢失的磷酸酶基因(phosphatase and tensinhomolog deleted on chromosome,PTEN)在胃腺癌及癌旁组织中的表达及其临床意义。方法:采用免疫组织化学S-P法检测FAK、p-FAK(Y397)和PTEN在100例胃腺癌和30例癌旁组织中的表达。结果:胃腺癌与癌旁组织FAK阳性表达率分别为71%(71/100)、43%(13/30)(P<0.05);P-FAK(Y397)阳性表达率分别为62%(62/100)、20%(6/30)(P<0.05);PTEN阳性表达率分别为53%(53/100)、97%(29/30)(P<0.05);癌组织中FAK、p-FAK(Y397)、PTEN的表达与胃腺癌分化程度、浸润深度、淋巴结转移及TNM分期有关(P<0.05),与年龄、性别无关(P>0.05);PTEN与FAK、P-FAK(Y397)在胃腺癌中的表达呈负相关(r=-0.514,-0.572;P<0.05),FAK与p-FAK(Y397)呈正相关(r=0.539;P<0.05)。结论:胃腺癌中存在FAK和p-FAK(Y397)表达上调,PTEN表达下调,三者的表达水平可能与胃腺癌的发生、发展有关。展开更多
基金supported by the National Natural Science Foundation of China Fund Project(82272956).
文摘Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.
基金supported by the National Natural Science Foundation of China(82002638)the National Natural Science Foundation of Sichuan Province(2023NSFSC0734).
文摘Background:Inhibitor of NF-κB kinase-interacting protein(IKIP)is known to promote proliferation of glioblastoma(GBM)cells,but how it affects migration and invasion by those cells is unclear.Methods:We compared levels of IKIP between glioma tissues and normal brain tissue in clinical samples and public databases.We examined the effects of IKIP overexpression and knockdown on the migration and invasion of GBM using transwell and wound healing assays,and we compared the transcriptomes under these different conditions to identify the molecular mechanisms involved.Results:Based on data from our clinical samples and from public databases,IKIP was overexpressed in GBM tumors,and its expression level correlated inversely with survival.IKIP overexpression in GBM cells inhibited migration and invasion in transwell and wound healing assays,whereas IKIP knockdown exerted the opposite effects.IKIP overexpression in GBM cells that were injected into mouse brain promoted tumor growth but inhibited tumor invasion of surrounding tissue.The effects of IKIP were associated with downregulation of THBS1 mRNA and concomitant inhibition of THBS1/FAK signaling.Conclusions:IKIP inhibits THBS1/FAK signaling to suppress migration and invasion of GBM cells.
文摘目的探究FAK/Twist1信号通路在颅缝闭合过程中的作用。方法将10 d大鼠分为对照组(50只)和颅缝旋转组(50只),以大鼠人字缝中点为中心,直径约0.5 cm做一骨窗,将骨瓣在不损伤硬脑膜的情况下游离,对照组骨瓣原位复位,旋转组骨瓣旋转180°后复位,两组大鼠3周后进行实验。旷场试验测试行为学,测量两组体质量、头围、骨瓣面积、骨瓣厚度等生理学指标,显微镜及HE染色观察颅缝闭合情况,Western blot、Real time PCR、免疫组化染色测定骨瓣及骨瓣下硬脑膜FAK/Twist1通过表达情况。结果旋转组骨瓣厚度大于对照组,差异有统计学意义(P<0.01),头围、体质量、骨瓣面积、术区面积无明显差异;显微镜下及HE染色中结果显示:旋转组颅缝完全闭合,对照组颅缝保持正常形态;行为学试验结果显示,颅缝闭合后大鼠行动能力下降且出现抑郁倾向;Western blot、Real time PCR、免疫组化染色显示:旋转组FAK在颅骨和硬脑膜中表达量均高于对照组且差异有统计学意义(P<0.05),旋转组Twist1在硬脑膜中表达量低于对照组且差异有统计学意义(P<0.05),在颅骨中两组Twist1表达量相近,差异无统计学意义。结论颅缝旋转后可以导致颅缝早闭,并会出现行动能力下降等行为学异常,FAK/Twist1可能在颅缝闭合过程中发挥着重要作用。
文摘目的:研究粘着斑激酶(focal adhesion kinase,FAK)、磷酸化粘着斑激酶(phospho-FAK,Y397)、与张力蛋白同源的第10号染色体丢失的磷酸酶基因(phosphatase and tensinhomolog deleted on chromosome,PTEN)在胃腺癌及癌旁组织中的表达及其临床意义。方法:采用免疫组织化学S-P法检测FAK、p-FAK(Y397)和PTEN在100例胃腺癌和30例癌旁组织中的表达。结果:胃腺癌与癌旁组织FAK阳性表达率分别为71%(71/100)、43%(13/30)(P<0.05);P-FAK(Y397)阳性表达率分别为62%(62/100)、20%(6/30)(P<0.05);PTEN阳性表达率分别为53%(53/100)、97%(29/30)(P<0.05);癌组织中FAK、p-FAK(Y397)、PTEN的表达与胃腺癌分化程度、浸润深度、淋巴结转移及TNM分期有关(P<0.05),与年龄、性别无关(P>0.05);PTEN与FAK、P-FAK(Y397)在胃腺癌中的表达呈负相关(r=-0.514,-0.572;P<0.05),FAK与p-FAK(Y397)呈正相关(r=0.539;P<0.05)。结论:胃腺癌中存在FAK和p-FAK(Y397)表达上调,PTEN表达下调,三者的表达水平可能与胃腺癌的发生、发展有关。
