Immune-related long noncoding RNA zinc finger protein 710-AS1-201 promotes the metastasis and invasion of gastric cancer cells

BACKGROUND Gastric cancer(GC)is a prevalent malignant tumor of the gastrointestinal system.ZNF710 is a transcription factor(TF),and zinc finger protein 710(ZNF710)-AS1-201 is an immune-related long noncoding RNA(lncRNA)that is upregulated in GC cells.AIM To assess the correlation between ZNF710-AS1-201 and immune microenvir-onment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells.METHODS We obtained data from The Cancer Genome Atlas and Wujin Hospital.We assessed cell growth,migration,invasion,and programmed cell death using cell counting kit-8,EdU,scratch,Transwell,and flow cytometry assays.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to identify the potential downstream targets of ZNF710-AS1-201.RESULTS In GC tissues with low ZNF710-AS1-201 expression,immunoassays detected significant infiltration of various antitumor immune cells,such as memory CD8 T cells and activated CD4 T cells.In the low-expression group,the half-maximal inhibitory concentrations(IC_(50)s)of 5-fluorouracil,cisplatin,gemcitabine,and trametinib were lower,whereas the IC_(50)s of dasatinib and vorinostat were higher.The malignant degree of GC was higher and the stage was later in the high-expression group.Additionally,patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates.In vitro,the overexpression of ZNF710-AS1-201 greatly enhanced growth,metastasis,and infiltration while suppressing cell death in HGC-27 cells.In contrast,the reduced expression of ZNF710-AS1-201 greatly hindered cell growth,enhanced apoptosis,and suppressed the metastasis and invasion of MKN-45 cells.The expression changes in ZNF710 were significant,but the corresponding changes in isocitrate dehydrogenase-2,Semaphorin 4B,ARHGAP10,RGMB,hsa-miR-93-5p,and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201,as determined by qRT-PCR.CONCLUSION Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells.It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC.Nevertheless,it is still necessary to determine the specific targets of the ZNF710 TF.

Correlation between TEX14 and ADAM17 expressions in colorectal cancer tissues of elderly patients and neoplasm staging,invasion,and metastasis

BACKGROUND Colorectal cancer(CRC)is one of the most frequently encountered malignant tumors in clinical settings.Proteins encoded by the testis-expressed gene 14(TEX14)are imperative for spermatogenesis,necessitating intercellular bridges between germ cells.Anomalous expression of TEX14 has also been associated with the proliferation and differentiation of certain tumor cells.Recombinant A disintegrin and metalloprotease 17(ADAM17)is known as a membrane-bound protease that regulates cellular activities and signal transduction by hydrolyzing various substrate proteins on the cell membrane.We hypothesize that TEX14 and ADAM17 may serve as potential biomarkers influencing the staging,invasion,and metastasis of CRC.AIM To probe the correlation between TEX17 and ADAM17 profiles in the CRC tissues of elderly patients and their association with CRC staging,invasion,and metastasis.METHODS We gathered data from 86 elderly patients diagnosed pathologically with CRC between April 2020 and December 2023.For each patient,one sample of cancer tissue and one sample of adjacent normal tissue were harvested.Real-time fluorescence quantitative PCR measured the mRNA profiles of TEX14 and ADAM17.Immunohistochemistry ascertained the positivity rates of TEX14 and ADAM17 expressions.Clinical pathological features of neoplasm staging,invasion,and metastasis were collected,and the association between TEX14 and ADAM17 expressions and clinical pathology was evaluated.RESULTS The mRNA and expression profiles of TEX14 and ADAM17 were significantly elevated in CRC tissues.The positivity rates of TEX14 and ADAM17 proteins in CRC tissues were 70.93%and 77.91%,respectively.There were no significant differences in age,sex,pathological type,and tumor diameter between TEX14 and ADAM17-positive and-negative patients.Patients with higher tumor differentiation degree,deeper infiltration and TNM stages ranging from III to IV exhibited higher positivity rates of TEX14 and ADAM17.Patients with lymph node metastasis and distant metastasis showed higher positivity rates of TEX14 and ADAM17 than those without.Positive expressions of TEX14 and ADAM17 were highly correlated with tumor staging,invasion,and metastasis.CONCLUSION TEX14 and ADAM17 profiles were significantly elevated in the CRC tissues of elderly patients,and their high expressions were associated with tumor staging,invasion,and metastasis.

Risk factors for lymph node metastasis and invasion depth in early gastric cancer:Analysis of 210 cases

BACKGROUND Gastric cancer is the leading cause of cancer-related deaths worldwide.Early gastric cancer(EGC)is often associated with the risk of lymph node metastasis,which influences treatment decisions.Despite the use of enhanced computed tomography,the prediction of lymph node involvement remains challenging.AIM To investigate the risk factors for lymph node metastasis and invasion depth in patients with EGC.METHODS In total,210 patients with pathologically diagnosed EGC were included in this study.Univariate and multivariate statistical analyses were used to predict risk factors for lymph node metastasis and invasion depth in patients with EGC.RESULTS Among the 210 patients,27(12.9%)had lymph node metastases.Of the 117 patients with submucosal gastric cancer,24(20.5%)had lymph node metastases.Both univariate and multivariate analyses indicated that the depth of invasion in EGC was a risk factor for lymph node metastasis in these patients.Additionally,pathological type was identified as a risk factor for cancer cell invasion in patients with EGC.CONCLUSION EGC invasion depth,not tumor type,size,age,sex,or location,predicts lymph node spread.Tumor type,not size,age,sex,or location,predicts cancer cell invasion.

Expression of MAPK1 in cervical cancer and effect of MAPK1 gene silencing on epithelial-mesenchymal transition,invasion and metastasis

Objective:To discuss the expression of mitogen-activated protein kinase 1(MAPK1) in the cervical cancer and effect of MAPK1 gene silencing on epithelial-mesenchymal transition and invasion and metastasis.Methods:Immunohistoehemistry,western blot and RT-PCR method were employed to detect the expression of MAPKl protein and mRNA in cervical cancer tissue and adjacent normal tissue.The constructed siRNA-MAPKI was transferred into human cervical cancer HeLa cells using Lipofectamine^(?)2000.MTT method was used to detect the cell vitality,transwell method to detect the cell invasion,and western blot to detect the expression of matrix metalloproteinases(MMP)-2,MMP-9,tissue inhibitor of metalloproteinase(TIMP)-1,TIMP-2,zinc finger transcription factor(Snail),epithelialmesenchymal transition related protein(EMT) E-cadherin and vimentin in cells.Results:The expression of MAPKl protein and mRNA in the cervical cancer tissue was significantly higher than the one in the adjacent normal tissue(P<0.01):after transfecting the siRNA-MAPKI into the human cervical cancer HeLa cells through liposome,compared with the control group,its cell vitality was significantly decreased(P<0.01),cell invasion was significantly decreased(P<0.01);expressed of MMP2.MMP-9,Snail and vimentin was significantly decreased(P<0.01),and expression of TIMP-1,TIMP-2 and E-cadherin was significantly increased(/J<0.01).Conclusions:Because of the high expression of MAPKl in the cervical cancer tissue,the interference in the expression of MAPK1 can significantly inhibit the invasion and metastasis of cervical cancer HeLa cells,which is related to the interference in the expression of MMPs/TIMP and Snail-mediated generation of EMT.

Effect of salinomycin on metastasis and invasion of bladder cancer cell line T24

Objective: To explore the effect of salinomycin on the metastasis and invasion of bladder cancer cell line T24 by regulating the related protein expression in the process of epithelialmesenchymal transition(EMT), and to provide experimental basis for the treatment of urological tumors. Methods: The bladder cancer cell line T24 was cultured in vitro. The rat bladder tumor model was established in vivo. The rats were randomized into two groups, among which the rats in the experiment group were given intraperitoneal injection of salinomycin, while the rats in the control group were given intraperitoneal injection of normal saline. The change of tumor cells in the two groups was observed. Transwell was used to detect the cell migration and invasion abilities, Real-time PCR was used to detect the expression of m RNA, while Western-blot was utilized for the determination of the expressions of E-cadherin and vimentin proteins. Results: The metastasis and invasion abilities of serum bladder cancer cell line T24 after salinomycin treatment in the experiment group were significantly reduced when compared with those in the control group, and the tumor metastasis lesions were decreased from an average of 1.59 to 0.6(P<0.05). T24 cell proliferation in the experiment group was gradually decreasing. T24 cell proliferation at 48 h was significantly lower than that at 12 h and 24 h(P<0.05). T24 cell proliferation at 24 h was significantly lower than that at 12 h(P<0.05). T24 cell proliferation at each timing point in the experiment group was significantly lower than that in the control group(P<0.05). The serum m RNA level and E-cadherin expression in the tumor tissues in the experiment group were significantly higher than those in the control group, while vimentin expression level was significantly lower than that in the control group(P<0.05). Conclusions: Salinomycin can suppress the metastasis and invasion of bladder cancer cells, of which the mechanism is probably associated with the inhibition of EMT of tumor cells.

Relationship between CYP1A1 polymorphisms and invasion and metastasis of breast cancer

Objective:To investigate the relationship between CYPIA1 genetic polymorphisms and the invasion and metastasis of breast cancer.Methods:The CYP1A1 gene polymorphism(an T-C transversion at nucleotide position 3801)was detected by the polymerase chain reaction and restriction fragment length polymorphism in 80 cases with breast cancer and 60 samples of normal breast tissue.The difference in genotypic distribution frequency between the groups,the correlation between the genotypes and the factors related to prognosis were analyzed.Results:The incidence of homozygous and variant genotypes had no difference between the breast cancer group and controls group(P=0.746).The proportion of variant genotype increased as clinical stage(P=0.006)advanced,as well as with increased numbers of lymph node metastases(P=0.010).Conclusions:In patients with breast cancer there is a correlation between the CYP1A1 CC allele and some factors indicating poor prognosis,including more lymph node metastases as well as a more advanced clinical stage.

Effects of Inhibiting JAK on Invasion and Metastasis of the Human Breast Cancer Cells through ERK Signaling Transduction Pathway

Objective： To explore the effects of Janus activated kinase （JAK） inhibitor AG490 on the phosphorylation of extracellular signal regulated protein kinase （ERK） in human breast cancer cells MDA-MB-231 and the roles of JAK in the invasion and metastasis of the human breast cancer cells through ERK signaling transduction pathways. Methods： MDA-MB-231 cells were treated with 20 μmol/L, 40 μmol/L, 80 μmol/L Janus kinase inhibitor AG490 for 24, 48 and 72 h. Proliferation and adhesion of MDA-MB-231 cells to matrigel were measured with MTT assay. When treated with 40 μmol/L AG490 for 24 h, the expressions of P-ERK and MMP-9 of cells were detected by Western-blot and invasion and metastasis of MDA-MB-231 cells were evaluated with transwell chamber. Results： After being treated with 20 μmol/L, 40 μ/L, 80 μmol/L AG490 for 24, 48 and 72 h, the proliferation of MDA-MB-231 cells was inhibited in a dose-and time-dependent manner. MDA-MB-231 cells treated with 40 μmol/L AG490 for 30, 60, 90 and 120 rain resulted in the increasing adhesion of cells to Matrigel in a time-dependent manner. However, capacity of adhesion in the group treated with AG490 was significantly decreased in comparison with the control group （P〈0.01）. The expression level of P-ERK and MMP-9 were decreased when treated with AG490. After treatment with 40 μmol/L AG490, in invasion assay, the number of cells in AG490 treated group to migrate to filter coated with Matrigel was reduced compared with control group （P〈0.05） Meanwhile, in migration assay, the number of cells in AG490 treated group to migrate to filter was also decreased compared with control group （P〈0.05）. Conclusion： Our study indicates that JAK kinase could affect the activity of ERK signal transduction pathway through the phosphorylation of ERK. The inhibitory effects of JAK kinase on MMP-9 expression and invasion of breast cancer cells were associated with the down-regulation of the ERK signaling pathway.

Effects of Curcumin on Invasion and Metastasis in the Human Cervical Cancer Cells Caski

Objective： To explore the effects of curcumin on invasion and metastasis in the human cervical cancer cells Caski. Methods： Caski cells were treated with 10, 25, 50tamol/L curcumin for 24, 48, 72 h. Proliferation of Caski cells was measured with MTT assay. When treated with 50pmol/L curcumin for 72 h, the expressions of MMP-2, MT1-MMP and NF-κB of cells were detected by Western-blot, and invasion and metastasis of Caski cells were evaluated with transwell chamber. Results： After being treated with 10μmol/L, 251xmol/L, 50μmol/L curcumin for 24, 48 and 72 h, the proliferation of Caski cells was inhibited in a dose-and time-dependent manner. The expression of MMP-2, MT1-MMP and NF-nB were decreased when being treated with 50μmol/L curcumin for 72 h. After treatment with 50μmol/L curcumin, in invasion assay, the number of cells in curcumin treated group to migrate to filter coated with Matrigel was reduced compared with control group（P〈0.05）. Meanwhile, in migration assay, the number of cells in curcumin treated group to migrate to filter was also decreased compared with control group （P〈0.05）. Conclusion： Curcumin could affect the invasion and metastasis of the human cervical cancer cells Caski. Inhibiting the expression of MMP-2, MT1-MMP and NF-κB was probably one of its molecular mechanisms.

Effects of Neuregulins on Invasion and Metastasis of Non-overexpression ErbB2 Breast Cancer Cells

Objective： To explore the effects of neuregulins on ErbB2 receptor signal transduction pathway activation, and invasion and metastasis of non-overexpression ErbB2 breast cancer cell MDA-MB-231. Methods： The expressions of neuregulin were detected by immunocytochemistry and Western blot. MDA-MB-231 cells were treated with ErbB2 kinase inhibitor AG825. Proliferations were measured with MTT assay. Invasion and metastasis of MDA-ME-231 cells were evaluated with transwell chamber. The enzyme activities of MMP-2 and MMP-9 were detected by gelatin zymography. The expressions of MMP-2 and HIF-1α were detected by Western blot. Results： MDA-MB-231 cells expressed a relatively higher level of neuregulin. In Western blot, the positive reaction band was found at 44KD which coincides with the molecular weight of NRG. When MDA-MB-231 cells were treated with AG825, the proliferation was inhibited in a time-dose-dependent manner （P〈0.01）, invasion and metastasis were also depressed （P〈0.05）. The enzyme activities of MMP-2 and MMP-9 were lower （P〈0.05）. The expression levels of MMP-2 and HIF-lct were decreased （P〈0.05）. Conclusion： Our study indicates that neuregulins are synthesized in MDA-MB-231 cells as transmembrane proteins, neuregulins could activate ErbB2 receptor signal transduction pathway by autocrine or paracrine secretion, and induce invasion and metastasis of MDA-MB-231 cells.

Inhibitory Effect of Coxsackie Adenovirus Receptor on Invasion and Metastasis Phenotype of Ovarian Cancer Cell Line SKOV3

Full-length coxsackie adenovirus receptor (CAR) eukaryotic expression plasmid was transfected into an ovarian cell line, SKOV3, and its effect on the change of malignant metastasis phenotype was explored. CAR mRNA and protein expression levels among 4 ovarian cancer cell lines (A2780, SKOV3, SW626, CAOV3) and the positive control 293 (a transformed human embryo kidney cell line) was detected by using semi-quantitative RT-RCR and Western blot and compared. CAR-negative SKOV3 was transfected with the eukaryotic expression plasmid containing a full-length CAR cDNA and mock-vector respectively. The positive clones were screened by G418. The biological behavior changes of positive transfected cells were gauged by colony formation in soft agar assay and cell adhesion assay. Among the cell lines, there were obviously different CAR expression levels. CAR could not be detected in SKOV3. In transfected cell group, CAR expression was enhanced obviously as compared with non-transfected or mock-transfected groups. Cell adhesion in the transfected group was promoted. The number of colony formation was reduced significantly in transfected groups (25.32±8.91) as compared with that in non-transfected group (88.75±13.98) and mock-transfected group (82.53±19.37). Among the 4 ovarian cancer cell lines, CAR expression level was variable. Exogenous CAR expression had a potential role in inhibiting the malignant metastasis phenotype of ovary cancer cells.

LINC01268 promotes epithelial-mesenchymal transition,invasion and metastasis of gastric cancer via the PI3K/Akt signaling pathway and targeting MARCKS

BACKGROUND Long non-coding RNAs(lncRNAs)with differential expression characteristics have been found to be closely related to the tumorigenesis and development of gastric cancer(GC),but their specific mechanisms and roles still need to be further elucidated.AIM To investigate the expression of LINC01268 in GC and its mechanism of affecting GC progression.METHODS Real-time quantitative polymerase chain reaction was used to detect the expression of LINC01268 in GC tissues,cell lines and plasma.The Kaplan-Meier method was used to evaluate the value of LINC01268 in the prognostication of GC patients.An receiver operating characteristic curve was constructed to evaluate the value of LINC01268 in the diagnosis of GC.Transwell migration and invasion assays and wound healing assays were used to confirm the effect of LINC01268 on the invasion and migration of GC cells.The regulatory relationship between LINC01268 and myristoylated alanine rich protein kinase C substrate(MARCKS),the PI3K/Akt signaling pathway,and the epithelial-mesenchymal transition(EMT)process in GC was demonstrated by western blot analysis.RESULTS The expression of LINC01268 was increased in GC tissues and cell lines.The expression level of LINC01268 was significantly correlated with lymph node metastasis,TNM stage,and tumor differentiation in patients with GC.Over-expression of LINC01268 indicated a poor prognosis for patients with GC,and it had a certain auxiliary diagnostic value for GC.In vitro functional experiments proved that the abnormal expression of LINC01268 further activated the PI3K/Akt signaling pathway and promoted EMT by targeting and regulating MARCKS and ultimately promoted the invasion and metastasis of GC.CONCLUSION This study elucidates that LINC01268 in GC may be an oncogene that further activates the PI3K/Akt signaling pathway and EMT by targeting and regulating MARCKS,and ultimately promotes the invasion and metastasis of GC.LINC01268 may be a potential effective target for the treatment of GC.

Histological Risk Factors for Lymph Node Metastasis in pT1 Colorectal Cancer:Does Submucosal Invasion Depth Really Matter?

Objective After endoscopic resection of colorectal cancer with submucosal invasion(pT1 CRC),additional surgical treatment is recommended if deep submucosal invasion(DSI)is present.This study aimed to further elucidate the risk factors for lymph node metastasis(LNM)in patients with pT1 CRC,especially the effect of DSI on LNM.Methods Patients with pT1 CRC who underwent lymph node dissection were selected.The Chi-square test and multivariate logistic regression were used to analyze the relationship between clinicopathological characteristics and LNM.The submucosal invasion depth(SID)was measured via 4 methods and analyzed with 3 cut-off values.Results Twenty-eight of the 239 patients presented with LNM(11.7%),and the independent risk factors for LNM included high histological grade(P=0.003),lymphovascular invasion(LVI)(P=0.004),intermediate to high budding(Bd 2/3)(P=0.008),and cancer gland rupture(CGR)(P=0.008).Moreover,the SID,width of submucosal invasion(WSI),and area of submucosal invasion(ASI)were not significantly different.When one,two,three or more risk factors were identified,the LNM rates were 1.1%(1/95),12.5%(7/56),and 48.8%(20/41),respectively.Conclusion Indicators such as the SID,WSI,and ASI are not risk factors for LNM and are subjective in their measurement,which renders them relatively inconvenient to apply in clinical practice.In contrast,histological grade,LVI,tumor budding and CGR are relatively straightforward to identify and have been demonstrated to be statistically significant.It would be prudent to focus on these histological factors rather than subjective measurements.

Tumor-associated macrophages regulate gastric cancer cell invasion and metastasis through TGFβ2/NF-κB/Kindlin-2 axis

Objective: Recent studies have shown that tumor-associated macrophages(TAMs) play an important role in cancer invasion and metastasis. Our previous studies have reported that TAMs promote the invasion and metastasis of gastric cancer(GC) cells through the Kindlin-2 pathway. However, the mechanism needs to be clarified.Methods: THP-1 monocytes were induced by PMA/interleukin(IL)-4/IL-13 to establish an efficient TAM model in vitro and M2 macrophages were isolated via flow cytometry. A dual luciferase reporter system and chromatin immunoprecipitation(Ch IP) assay were used to investigate the mechanism of transforming growth factor β2(TGFβ2) regulating Kindlin-2 expression. Immunohistochemistry was used to study the relationships among TAM infiltration in human GC tissues, Kindlin-2 protein expression, clinicopathological parameters and prognosis in human GC tissues. A nude mouse oncogenesis model was used to verify the invasion and metastasis mechanisms in vivo.Results: We found that Kindlin-2 expression was upregulated at both m RNA and protein levels in GC cells cocultured with TAMs, associated with higher invasion rate. Kindlin-2 knockdown reduced the invasion rate of GC cells under coculture condition. TGFβ2 secreted by TAMs regulated the expression of Kindlin-2 through the transcription factor NF-кB. TAMs thus participated in the progression of GC through the TGFβ2/NF-κB/Kindlin-2 axis. Kindlin-2 expression and TAM infiltration were significantly positively correlated with TNM stage, and patients with high Kindlin-2 expression had significantly poorer overall survival than patients with low Kindlin-2 expression. Furthermore, Kindlin-2 promoted the invasion of GC cells in vivo.Conclusions: This study elucidates the mechanism of TAMs participating in GC cell invasion and metastasis through the TGFβ2/NF-κB/Kindlin-2 axis, providing a possibility for new treatment options and approaches.

Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells

AIM: To study the effect of the transfected Twist gene on invasion and metastasis of gastric carcinoma cells and the possible mechanisms involved. METHODS: Human gastric carcinoma MKN28 cells were stably transfected with Twist sense plasmid, and MKN45 cells were stably transfected with Twist antisense plasmid using the lipofectamine transfection technique. RT-PCR, Western blotting, EMSA, gelatin zymography assay, and in vitro invasion and migration assays were performed. Nude mice metastasis models were established by the abdominal cavity transfer method. RESULTS: Cell models (TwistS-MKN28) that steadily expressed high Twist protein were obtained. Compared with MKN28 and pcDNA3-MKN28 cells, adherence, migration and invasion ability of TwistS -MKN28 cells were clearly raised. The number of cancer nodules was increased significantly in the abdominal cavity and liver of nude mice inoculated with TwistS-MKN28 cells. Overexpression of Twist in MKN28 cells increased Tcf-4/ Lef DNA binding activity, and promoted expression of Tcf-4’s downstream target genes cyclin D1 and MMP-2. However, suppression of Twist (TwistAS-MKN45) inhibited MKN45 cell invasion and the expression of cyclin D1 was reduced. The activity of MMP-2 was also decreased. CONCLUSION: These results indicate that Twist promotes gastric cancer cell migration, invasion and metastasis, and Twist may play an important role in Wnt/ Tcf-4 signaling.

Higher CO_2-insufflation pressure inhibits the expression of adhesion molecules and the invasion potential of colon cancer cells

AIM： To investigate the influence of CO2-insufflation pressure on adhesion, invasion and metastatic potential of colon cancer cells based on adhesion molecules expression. METHODS： With an/n vitro artificial pneumoperitoneum model, SW1116 human colon carcinoma cells were exposed to CO2-insufflation in 5 different pressure groups： 6 mmHg, 9 mmHg, 12 mmHg, 15 mmHg and control group, respectively for 1 h. Expression of E-cadherin, ICAM-I, CD44 and E-selectin was meas- ured at 0, 12, 24, 48 and 72 h after CO2-insufflation using flow cytometry. The adhesion and invasion capacity of SW1116 cells before and after exposure to CO2-insufflation was detected by cell adhesion/invasion assay in vitro. Each group of cells was injected intraperitoneally into 16 BALB/C mice. The number of visible abdominal cavity tumor nodules, visceral metas-tases and survival of the mice were recorded in each group. RESULTS： The expression of E-cadherin, ICAM-1, CD44 and E-selectin in SWl116 cells were changed significantly following exposure to CO2 insufflation at different pressures （P 〈 0.05）. The expression of E-cadherin, CD44 and ICAM-1 decreased with increasing CO2-insufflation pressure. The adhesive/ invasive cells also decreased gradually with increasing pressure as determined by the adhesion/invasion assay. In animal experiments, the number of abdominal cavity tumor nodules in the 15 mmHg group was also significantly lower than that in the 6 mmHg group （29.7± 9.91 vs 41.7±14.90, P = 0.046）. However, the survival in each group was not statistically different. CONCLUSION： CO2-insufflation induced a temporary change in the adhesion and invasion capacity of cancer cells in vitro. Higher CO2-insufflation pressure inhibited adhesion, invasion and metastatic potential in vitro and in vivo, which was associated with reduced expression of adhesion molecules.

Overexpression of HOXB9 promotes metastasis and indicates poor prognosis in colon cancer

Objective：Homeobox B9 （HOXB9） is proposed to be involved in tumor angiogenesis and metastasis.We investigated the role of HOXB9 in the progression of colon cancer.Methods：HOXB9 expression was investigated by immunohistochemically and Western blotting in 128 colon cancer patients and the results were analyzed statistically associated with clinicopathological data and survival of the patients.The effect of HOXB9 on cell invasion and metastases abilities were analyzed in vitro and in vivo.Results：HOXB9 is overexpressed in colon cancer tissues and significandy correlated with metastasis and poor survival of patients （P＜0.05,respectively）.Additionally,high levels of expression of HOXB9 were observed in metastatic lymph nodes.The down-regulation of HOXB9 expression can inhibit the migration and invasive ability of colon cancer cells,while exogenous expression of HOXB9 in colon cancer cells enhanced cell migration and invasiveness.Moreover,stable knockdown of HOXB9 reduced the liver and lung metastasis of colon cancer in vivo.Conclusions：HOXB9 may play an important role in the invasion and metastasis of colon cancer cells and may be a useful biomarker for metastasis and prognostic of colon cancer.

miR-374b-5p suppresses RECK expression and promotes gastric cancer cell invasion and metastasis

AIM: To profile expression of microRNAs (miRNAs) in gastric cancer cells and investigate the effect of miR-374b-5p on gastric cancer cell invasion and metastasis.

Calponin 3 promotes invasion and drug resistance of colon cancer cells

BACKGROUND Calponin 3(CNN3)is an actin-binding protein expressed in smooth muscle and non-smooth muscle cells.It is required for cytoskeletal rearrangement and wound healing.AIM To dissect the role of CNN3 in carcinogenesis with a focus on colon cancer.METHODS A total of 20 cancer cell lines(8 breast,11 colon,and HeLa cervical cancer cell as a positive control for mesenchymal phenotype)and 57 formalin-fixed,paraffinembedded sections from archived sporadic colorectal carcinomas were included in this study.CNN3 expression analysis by western blot or immunohistochemistry was followed by functional analyses.The CNN3 gene was silenced by specific small interfering RNA(commonly known as siRNA),followed by confirmation of the silencing efficiency by western blotting.Then,the silenced cells and control siRNA-transfected cells were analyzed for changes in epithelial and mesenchymal markers,invasion,and response to 5-fluoruracil treatment.We also performed proteomics analysis using a phospho-kinase array-based panel of 45 proteins.RESULTS CNN3 showed positive expression in 6/8 breast and 9/11 colon cancer lines and in HeLa cells.Interestingly,the colorectal adenocarcinoma line SW480 was negative,while the cell line developed from its matching lymph node metastasis(SW620)was positive for CNN3.CNN3 expression was fairly consistent with the metastatic phenotype in colon cancer because it was absent in one other colon cell line from a primary site and expressed in all others.We selected SW620 for subsequent functional analyses.CNN3-silenced SW620 cells showed a reduction in collagen invasion and loss of mesenchymal markers.CNN3 silencing caused an increase in the SW620 colon cancer cell sensitivity to 5-fluorouracil.Phosphokinase array-based proteomics analysis showed that CNN3 silencing in SW620 reduced extracellular signal-regulated kinase,β-Catenin,mutant p53,c-Jun,and heat shock protein 60 activities but increased that of checkpoint kinase 2.CNN3 was expressed in 20/57(35%)colon cancer cases as shown by immunohistochemistry.CNN3 was associated with a decrease in overall survival in colon cancer in silico.CONCLUSION These results show the involvement of CNN3 in lymph node metastasis and resistance to chemotherapy in colon cancer and suggest that significant oncogenic pathways are involved in these CNN3-related actions.

Effects of mTOR-STAT3 on the migra=tion and invasion abilities of hepatoma cell and mTOR-STAT3 expression in liver cancer

Objective:To investigate the effects of mT0R-STAT3 pathway on the invasion and migration of hepatoma cell.Methods:mTOR and STAT3 expresssion in the hepatocellular carcinoma cell line HepG2 and normal liver cell line L02 were detected by reverse transcription PCR(RTPCR) and western blotting.The migration and invasion abilities of cells and expression of STAT3were detected by scratch adhesion test and transwell migration assays,after siRNA transfection blocking mTOR expression of HepG2 cells.Results:The HepG2 cells expression is higher compared with normal cells L02 expression.Western blotting assay showed the mTOR expression was blocked,while STAT3 expression was also decreased,after the siRNA transfection of HepC2cells.The migration(scratch adhesion test) and invasion(transwell assays) abilities of HepG2 cells which the mTOR expression was blocked by siRNA interference were significantly decreased(P<0.05).Conclusion:mT0RSTAT3 expression in hepatoma cells HepG2 was significantly higher than that in normal liver cells.mTOR blocking can reduce the expression of STAT3,which is also closely related to the invasion and metastasis of liver cancer cells.

Regulation of cancer cell migration and invasion by sphingosine-1-phosphate

Sphingosine-1-phosphate (S1P) is a bioactive sphingo-lipid that has been implicated in regulation of a number of cancer cell malignant behaviors, including cell proliferation, survival, chemotherapeutic resistance and angiogenesis. However, the effects of S1P on cancer cell migration, invasion and metastasis, are perhaps its most complex, due to the fact that, depending upon the S1P receptors that mediate its responses and the crosstalk with other signaling pathways, S1P can either positively or negatively regulate invasion. This review summarizes the effects of S1P on cancer cell invasion and the mechanisms by which it affects this important aspect of cancer cell behavior.