Chromokinesin KIF4A as a tumor suppressor by inhibiting cell invasion

Objective To investigate the role of bone marrow mesenchymal stem cells (BM-MSCs) in the invasion and metastasis of gastric cancer cells and to explore its mechanism. Methods SGC7901 and KATO-Ⅲ gastric cancer cells were co-cultured with BM-MSCs respectively, and the invasion ability of SGC7901 and KATO-Ⅲ gastric cancer cells were detected by Transwell assay. Secondly, CD133+ and CD133- cells were sorted from KATO-Ⅲ gastric cancers and co-cultured with BM-MSCs respectively to compare their changes in invasiveness. Meanwhile, the expressions of p-AKT and epithelial-mesenchymal transition(EMT) relative factors in gastric cancer cells were detected by Western-blot. The role of CD133 in BM-MSCs affecting the ability of invasion of gastric cancer cells was further vertified by the overexpression of CD133 in SGC7901 cells. SPSS17.0 software was used for statistical processing, and the stand deviation of the measurement data were expressed as the standard deviation, independent sample t test was conducted. Results The invasiveness of co-cultured SGC7901 and KATO-Ⅲ cells was significantly enhanced. The invasive ability of KATO-Ⅲ CD133+ cells co-cultured with BM-MSCs tended to increase more significantly than that of co-cultured CD133- cells[(259.0±24.0)vs(58.0±5.6), P<0.001]. The expressions of p-AKT, Snail and N-cadherin were significantly increased in co-cultured CD133+ cells (P=0.003, P=0.003, P=0.002), while the expression of E-cadherin was reduced (P=0.021). After co-cultured with BM-MSCs, the expression of E-cadherin was also reduced in CD133- cells (P=0.005), but the expressions of p-AKT, Snail and N-cadherin were no significantly changes (P=0.744, P=0.277, P=0.295). SGC7901 co-cultured with BM-MSC after overexpression of CD133 showed higher invasiveness than blank control group[(239.3±24.0) vs (103.3±15.5), P<0.001]. The expressions of p-AKT, Snail and N-cadherin were significantly increased when co-cultured with BM-MSCs in the group of CD133 overexpression (P=0.001, P=0.001, P=0.001), while the expression of E-cadherin was significantly decreased(P=0.003). The expressions of Snail and N-cadherin were also significantly increased after co-cultured with BM-MSCs in the blank control group (P=0.001, P=0.004), and the expression of E-cadherin was significantly decreased (P=0.018), while the expression of p-AKT was not significantly changed (P=0.193). Conclusions BM-MSCs can enhance the invasion and metastasis of gastric cancer cells by promoting the EMT of gastric cancer cells. CD133 may be involved in the regulation of EMT in gastric cancer cells through the PI3K/AKT signaling pathway. Key words: Stomach neoplasms; Mesenchymal stem cells; Bone marrow; Epithelial-mesenchymal transition; CD133

To examine the expression of cytokine-induced apoptosis inhibitor1 (CIAPIN1) in gastric cancer and normal mucosa tissues, and to investigate its effects on migration and invasion of gastric cancer cells. Immunohistochemistry was used to detect CIAPIN1 expression in 15 samples of normal gastric mucosa tissues, 148 samples of gastric cancer tissues (42 of non-metastasis gastric cancer tissues without other organs or lymph node metastasis, 106 of metastasis gastric cancer tissues with lymph node metastasis), and 37 samples of gastric cancer lymph node metastasis tissues. Association of CIAPIN1 expression with clinicopathological characteristics of gastric cancer was analyzed by Chi-square test. SGC-7901 cell lines of high CIAPIN1 expression and low CIAPIN1 expression were established. Transwell assay was applied to detect the invasion and migration of CIAPIN1-regulated gastric cancer cells. Positive rate of CIAPIN1 expression in gastric cancer tissues was lower than that in normal gastric mucosa tissues (41.2% vs. 86.7%, P=0.0008), and in metastasis gastric cancer tissues was also lower than that in non-metastasis gastric cancer tissues (34.9% vs. 71.4%, P=0.0000). Furthermore, the positive rate of CIAPIN1 expression was closely related to the TNM staging of gastric cancer (TNM stage I(, II( and III( were 55.0%, 53.5% and 24.4%, respectively, P=0.0037). But there was no significant difference of positive expressive rate between metastatic gastric cancer tissues and metastatic lymph node tissues(34.9% vs. 21.6%, P=0.3700). Transwell assay showed that up-regulated CIAPIN1 expression would significantly reduce, while down-regulated CIAPIN1 expression would significantly promote the invasion and migration of SGC-7901 cells (all P<0.05). Positive rate of CIAPIN1 expression is low in gastric cancer tissues and shows inhibition of invasion and migration of gastric cancer cells.

Objective To investigate the effects of microRNA (miRNA, miR)-877 on proliferation and invasion of SGC7901 gastric cancer cells. Methods The relative expression level of miR-877 in gastric cancer cell lines (SGC7901, MGC803, MKN-45, BSG823, HGC-27, AGS) and normal gastric cell line (GES-1) were measured by real-time quantitative polymerase chain reaction (Real-time PCR). MiR-877 agonist (miR-877 mimics) was synthesized. MiR-877 mimics and miR-877 negative control were transfected into SGC7901 cells by liposome Lipofectamine™ 2000. Cell proliferation ability was detected by cell counting kit-8 (CCK-8) assay. Cell invasion ability was evaluated by Transwell method. The expression of phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB, also called Akt), phosphorylated Akt (p-Akt) were detected by Western blotting. Results The relative expression level of miR-877 was significantly lower in gastric cancer cell lines SGC7901 (0.21±0.05), MGC803 (0.63±0.11), MKN-45 (0.35±0.07), BSG823 (0.49±0.08), HGC-27 (0.75±0.10), AGS (0.43±0.07) than that in GSE-1 cells (1.09±0.13, all P<0.05). The relative expression level of miR-877 in miR-877 mimics group (0.27±0.05) was significantly lower than that in negative control group (1.06±0.11, t=11.690, P<0.01). The results of CCK-8 assay showed that the absorbance value of miR-877 mimics group (1.59±0.09) was significantly lower than that of negative control group (2.28±0.11, t=4.746, P<0.01) after culturing 72 h. The results of Transwell assay revealed that cell invasion number in miR-877 mimics group (43.60±17.30) was significantly lower than that in negative control group (129.35±16.70, t=8.148, P<0.01). The results of Western blotting manifested that the expression level of PI3K, Akt, p-Akt in miR-877 mimics group were significantly lower than that in negative control group (all P<0.01). Conclusion MiR-877 could inhibit the proliferation and invasion of gastric cancer cells, which is involved in suppressing PI3K/AKt signaling pathway. Key words: Gastric cancer; MicroRNA-877; Proliferation; Invasion; Phosphatidylinositol-3-kinase/protein kinase B signaling pathway

Objective To observe the effect of down-regulation of E26 transformation-specific homologous factor (EHF) expression on the growth of gastric cancer cells. Methods Western blotting and real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) were used to detect the expression of EHF protein and mRNA in gastric cancer cell lines BGC823, SGC7901 and gastric mucosal epithelial cell line GES-1, respectively. Using the small interfering RNA (siRNA) interference technology, si-EHF-979 or control siRNA si-NC was transfected into gastric cancer cells BGC823 and SGC7901. The si-EHF-979 transfection group served as experimental group, and si-NC transfection group as control group. The methyl thiazol tetrazolium (MTT) assay was utilized to detect the proliferation of gastric cancer cells. The effect of EHF on the migration and invasion of gastric cancer cells was measured by Transwell assay. The gastric cancer cell BGC823 transfected with si-EHF-979 or si-NC was inoculated into the right axilla of nude mice to establish a nude mouse exenograft model. Results Compared with GES-1 cells, the expression levels of EHF in BGC823 and SGC7901 cells were significantly up-regulated, with the difference being statistically significant (P=0.001). The ability of gastric cancer cells to proliferate, migrate and invade after EHF gene knockdown was significantly inhibited. The nude mouse xenograft model showed that knockdown of EHF expression significantly inhibited tumor growth in vivo, the difference was statistically significant (P=0.001). Conclusion EHF is highly expressed in gastric cancer cell lines. Knockdown of EHF expression can inhibit the proliferation of gastric cancer cells. Key words: Gastric cancer; E26 transformation-specific homologous factor; Cell proliferation; Cell migration

Objective To investigate the expression of microRNA-101 (miRNA-101) in human gastric cancer, and to explore its effects on proliferation, migration and invasion of gastric cancer cell. Methods The expression of miRNA-101 in 28 human gastric cancer tissues, human gastric cell lines BGC-823, SGC-7901, MKN-45, AGS and human normal gastric epithelial cell line GES-1 were determined by real time polymerase chain reaction (PCR). Recombinant miRNA-101 adenovirus vector was constructed. The effects of miRNA-101 on gastric cancer proliferation was detected with cell proliferation assay. The ability of gastric cancer cell migration and invasion was assessed with Transwell assay. Gastric xenograft cancer model was established in BALB/c nude mice and the tumor size was compared. The t test was used for the statistical analysis. Results The expression of miRNA-101 in gastric cancer tissues was 0.661±0.396, which was lower than that of corresponding para carcinoma tissues (1.128±0.697), and the difference was statistically significant (t=10.091, P<0.01). The expression of miRNA-101 in normal gastric epithelial cell line GES-1 was higher than those of gastric cancer cell lines BGC-823, SGC-7901, MKN-45 and AGS. There was significant suppression role of miRNA-101 on MKN-45 cells proliferation, and which also had inhibition role on cell migration and invasion of gastric cancer cell lines BGC-823, SGC-7901, MKN-45 and AGS. At five weeks after MKN-45 gastric xenograft cancer nude mice model established, the tumor size of Ad-miRNA-101 group ((333.56±46.71) mm3) was smaller than that of Ad-enhanced green fluorescent protein (EGFP) group (806.41±51.83) mm3, and the difference was statistically significant (t=21.431, P<0.01). Conclusion In gastric tissues and cells, miRNA-101 is a tumor suppressive miRNA and its downregulated expression involved in the genesis and development of gastric cancer, which may be a new target of biological target therapy in gastric cancer. Key words: microRNAs; Stomach neoplasms; miRNA-101

Objective To detect the expression of pleomorphic adenoma gene like-2 (PLAGL2) in human gastric cancer and cell lines, and its role in cell invasion and epithelial-mesenchymal transition (EMT) and the molecular mechanism involved. Methods Fifteen cases of pathologically confirmed gastric cancer tissues and their adjacent normal tissues were collected during operation in our hospital from Jan. 10, 2016 to Mar. 20, 2018. Gastric cancer cell lines MKN-28, BGC-823, NCI-N87 and SGC-7901 were cultured. The expression levels of PLAGL2 in gastric cancer tissue samples and MKN-28, BGC-823, NCI-N87 and SGC-7901 cells were determined by real-time quantitative polymerase chain reaction (Real-time PCR) and Western blotting. After successful transfection with PLAGL2-small interfering RNA (siRNA) in SGC-7901 cells, the expression levels of PLAGL2 mRNA and protein were detected by Real-time PCR and Western blotting respectively. Cell invasion was detected by Transwell assay. The expression levels of N-cadherin, Vimentin and E-cadherin, which were EMT related markers, and Wnt/β-catenin related proteins were detected by Western blotting. After PLAGL2-siRNA SGC-7901 cells were treated with Wnt pathway agonist SKL2001 and inhibitor XAV939, the changes of cell invasion ability were retested by Transwell assay. Results The expression levels of PLAGL2 mRNA (1.11±0.27) and protein (0.98±0.26) in gastric cancer tissues were significantly higher than those in the adjacent tissues (mRNA: 0.37±0.10; protein: 0.28±0.11; t=-20.941, P<0.01; t=-20.186, P<0.01). The expression levels of PLAGL2 mRNA and protein in MKN-28, BGC-823, NCI-N87 and SGC-7901 were significantly higher than GES-1 cells (mRNA: t=-12.327, P<0.01; t=-19.812, P<0.01; t=-13.080, P<0.01; t=-15.218, P<0.01; protein: t=-11.816, P<0.01; t=-21.162, P<0.01; t=-14.517, P<0.01; t=-15.899, P<0.01). The expression levels of PLAGL2 mRNA and protein in SGC-7901 cells were significantly decreased after PLAGL2-siRNA transfection (mRNA: 2.10±0.29; protein: 1.96±0.27) as compared with control siRNA group (mRNA: 6.61±0.73; protein: 6.46±0.71; t=-1.000, P<0.01; t=-1.000, P<0.01). The number of invasive cells at 24, 48, 72 hin PLAGL2-siRNA transfection group [(30.75±5.74), (48.75±6.90) and (64.50±4.80) cells] was significantly less than in control siRNA group [(51.00±4.97), ( 75.75±4.92) and (132.50±5.57) cells; t=-1.000, P<0.05; t=-1.000, P<0.01; t=-1.000, P<0.01]. The expression of N-cadherin, Vimentin, β-catenin, matrix metalloproteinase (MMP)-7 and c-Myc proteins was significantly down-regulated, and that of E-cadherin protein was significantly up-regulated (t=-1.000, P<0.01; t=-1.000, P<0.01; t=-1.000, P<0.01; t=-1.000, P<0.01; t=-1.000, P<0.01; t=-8.205, P<0.01). SKL2001 could reverse the inhibitory effect on EMT and invasion of SGC-7901 cells after PLAGL2-siRNA transfection, while XAV939 enhanced the above effects of PLAGL2-siRNA. Conclusion PLAGL2 is highly-expressed in gastric cancer. Inhibition of PLAGL2 gene by siRNA can inhibit the invasion of gastric cancer cells probably by down-regulating the Wnt/β-catenin signaling pathway. Key words: Gastric cancer; Invasion; Pleomorphic adenoma gene like-2; Epithelial-mesenchymal transition; Wnt/β-cateninn signaling pathway

Objective To analyze the expression and role of ubiquitin specific peptidase 18 (USP18)in gastric cancer cells, and to investigate the relationship between the development of gastric cancer and USP18. Methods The levels of USP18 protein and mRNA expression in immortalized gastric mucosa epithelial GSE cell lines and gastric cancer cell lines (AGS, MKN45, MKN25, BGC823, BGC803, SGC7901) were detected by using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. The role of USP18 in the invasion and proliferation of gastric cancer cells was analyzed by using CCK8 and Transwell assays. Results The mRNA level of USP18 was lower in GSE cell lines than that in gastric cancer cells (F= 794.052, P < 0.000 1). In six gastric cancer cell lines, mRNA level of USP18 was relatively high in BGC823 (17.62±0.55) and BGC803 (13.52±0.50) cell lines, and low in MKN28 (1.40±0.17) and MKN45 cell lines (4.23±0.26). As for the protein level, the expression of USP18 was lowest in GSE cell line. In six gastric cancer cell lines, the expression of USP18 was the highest in more aggressive SGC7901 and BGC803 cell lines and the lowest in AGS and MKN45 cells. Compared with the control group, interference of USP18 decreased the invasion and proliferation abilities of SGC7901 and BGC803 cell lines (P < 0.01). Conclusion USP18 is highly expressed in more invasive gastric cancer cells, and the down-regulation of USP18 can suppress the invasion and proliferation of gastric cancer cells. Key words: Stomach neoplasms; Ubiquitin specific peptidase 18; Neoplasm invasiveness; Cell proliferation

miR-199a-3p targets ETNK1 to promote invasion and migration in gastric cancer cells and is associated with poor prognosis

Objective To explore the roles and mechanisms of Cadherin 17 (CDH17) in interleukin-10-induced invasion of gastric cancer cells. Methods We detected the invasion of MKN-45 gastric cancer cells induced by interleukin-10 through Transwell assay. CDH17 small interfering RNA (siRNA) was constructed and transfected in MKN-45 cells to inhibit CDH17 expression. We then compared the difference in cell invasion with or without CDH17 expression and detected the activation of corresponding signaling pathway by immunoblotting in response to interleukin-10. We additionally detected invasion of MKN-45 cell after inactivation of signaling by using its specific inhibitor. Results Western blotting and transwell assay revealed that interleukin-10 (100 ng/ml) significantly induced expression of CDH17 in MKN-45 cells (P=0.021) and promoted its invasion (10 250±1 500 vs. 2 750±450, P=0.019) as well as activated phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway (P=0.041). After successful inhibition of CDH17 expression by siRNA, the interleukin-10-indueced invasion of MKN-45 cells was significantly reduced (10 250±1 500 vs. 2 325±300, P=0.027) and the activation of PI3K/Akt signaling pathway was also suppressed. Furthermore, preincubation of Ly294002 (10 nmol/L), the specific inhibitor of PI3K/Akt signaling pathway, not only prohibit the activation of PI3K/Akt signaling pathway but also obviously diminished interleukin-10-induced invasion of MKN-45 cells (2 050±400 vs. 11 500±1 750, P=0.016). Conclusion Interleukin-10-promoted invasion of MKN-45 gastric cancer cells is mediated by CDH17 through PI3K/Akt signaling pathway. Key words: Interleukin-10; Gastric cancer cells; Cadherin 17; Phosphoinositide-3-kinase signaling; Invasion

Background and aim: The novel gene psiTPTE22-HERV identified by us previously is a human endogenous retrovirus (HERV)-related gene located adjacent to the gene psiTPTE22. With a high GC content around the promoter region, expression of psiTPTE22-HERV can be regulated epigentically by DNA methylation. We aimed to elucidate the clinical significance of epigenetic alteration and biological function of psiTPTE22-HERV in gastric cancer. Methods and results: psiTPTE22-HERV was ubiquitously expressed in normal adult tissues including stomach, but was frequently silenced/down-reguated in gastric tumors and cancer cell lines as evidenced by RT-PCR. Bisulfite genomic sequencing results indicated that psiTPTE22-HERV was silenced by promoter DNA methylation, and its expression could be restored by demethylation treatments in gastric cancer cell lines. Ectopic expression of psiTPTE22-HERV significantly suppressed cell viability, clonogenicity and cell cycle progression, induced apoptosis, and inhibited migration and invasion of SGC7901 and MKN45 gastric cancer cells. In contrast, knock-down of psiTPTE22-HERV in the gastric cancer MKN1 cells significantly increased cell growth and migration ability, promoted cell cycle progress and inhibited cell apoptosis. psiTPTE22-HERV significantly suppressed subcutaneous tumorigenicity of SGC7901 cells in nude mice and metastasis (liver implantation) in tail vein injection models. Promoter methylation level of psiTPTE22-HERV was significantly higher in gastric tumors than in adjacent non-tumor tissues as revealed by bisulfite genomic sequencing (P&amp;lt;0.05); methylation levels in both tumors and adjacent non-tumor tissues of gastric cancer patients were significantly higher than in normal stomach tissues (both P&amp;lt;0.001). Multivariate Cox regression analysis demonstrated that promoter methylation of psiTPTE22-HERV in primary gastric tumors was an independent risk factor for poor survival. Kaplan-Meier survival curves showed that high-methylation of psiTPTE22-HERV promoter was significantly associated with shortened survival in gastric cancer patients from two independent cohorts (both P&amp;lt;0.05). Conclusion: psiTPTE22-HERV functions as a tumor suppressor that is commonly down-regulated by promoter methylation in gastric cancer, which may serve as a prognostic biomarker for gastirc cancer patients. Citation Format: Jessie Qiaoyi Liang, Fei Xu, Shu Zheng, Jun Yu. psiTPTE22-HERV functions as a tumor suppressor in gastric cancer and is associated with disease outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5519. doi:10.1158/1538-7445.AM2017-5519

Objective To investigate the expression of CYP2W1 in gastric cancer and its effect on proliferation and invasion. Methods CYP2W1 protein expression in 326 gastric cancertissues and in the corresponding normal gastric mucosa was measured by immunohistochemstry. The expression of CYP2W1 mRNA in 10 randomly chosen gastric cancer tissues and its corresponding normal gastric mucosa was tested by semi-quantitative RT-PCR. 4 groups pairs of gastric cancer and normal gastric mucosa cell lines were constructed. CYP2W1 expression in each of the cell line was tested. The effect of CYP2W1 expression on the proliferation and invasion capacity of the gastric cancer cells was studied by MTT experiment and transwell cell experiment. Results Expression of CYP2W1 protein in the gastric cancer tissues is higher than that in normal gastric mucosa (26.7% vs.0, χ2=100.396, P< 0.05). CYP2W1 mRNA in the gastric cancer tissues is higher than that in normal gastric mucosa [(0.413±0.026) vs.(0.074±0.005), t=28.115, P<0.05]. CYP2W1 protein expression in the gastric cancer cell lines is higher than that in normal gastric mucosa cell lines[(0.481±0.024) vs.0, t=49.097, P<0.05]. The growth capacity of CYP2W1 positive gastric cancer cell is stronger than that of CYP2W1 negative cells (P<0.05), and CYP2W1 positive gastric cancer cells are also more of invasiveness, [(63±8) vs. (18±3), t=24.134, P<0.05]. Conclusions CYP2W1 is only expressed in the gastric cancer tissues, hence it is closely related to the growth multiplication, and invasiveness of gastric cancer cells. Key words: Stomach neoplasm; Cell proliferation; Neoplasm invasiveness

ObjectivePrevious studies suggested that sevoflurane exerts anti-proliferative, anti-migratory, and anti-invasive effects on cancer cells. To determine the role of sevoflurane on gastric cancer (GC) progression, we evaluated its effects on the proliferation, migration, and invasion of SGC7901, AGS, and MGC803 GC cells.MethodsGC cells were exposed to different concentrations of sevoflurane (1.7, 3.4, or 5.1% v/v). Cell viability, migration, and invasion were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays. Immunohistochemical staining and immunoblotting were performed to analyze forkhead box protein 3 (FOXP3) protein expression in tissue specimens and cell lines, respectively.ResultsFOXP3 was downregulated in human GC specimens and cell lines. Functionally, FOXP3 overexpression significantly inhibited the proliferation, migration, and invasion of GC cells and accelerated their apoptosis. Moreover, sevoflurane significantly blocked GC cell migration and invasion compared with the findings in the control group. However, FOXP3 silencing neutralized sevoflurane-induced apoptosis and the inhibition of GC cell migration and invasion. Sevoflurane-induced apoptosis and the suppression of migration and invasion might be associated with FOXP3 overactivation in GC cells.ConclusionsSevoflurane activated FOXP3 and prevented GC progression via inhibiting cell migration and invasion in vitro.

Phosphorylation of Ephrin-B1 Regulates Dissemination of Gastric Scirrhous Carcinoma

Objective To study the effects of tumor-associated calcium signal transducer-2 (TROP-2) gene small interfering RNA (siRNA) on adhesion, migration, and invasion of human gastric cancer cells.Methods Real time polymerase chain reaction (PCR) was used to detect the TROP-2 mRNA expression of human gastric cancer cell lines MGC-803, HC, C-27 and BGC-823. The cells with highest expression of TROP-2 were transfected with different doses of TROP-2 siRNA. The expression of TROP-2 mRNA and protein was detected by real-time quantitative PCR and immumoflureseence method. Cell adhesion, migration,and invasion were exmined by hoyden chamber, respectively. Results Cell line BGC-823 showed the highest elevation of TROP-2 mRNA among three gastric cancer cell lines. Real-time quantitative PCR and immumoflurescence method revealed that the expression of TROP-2 mRNA and protein was reduced in a time- and dose-dependent manner ( r = 0. 935 ; r = 0. 922). The ability of adhesion, migration and invasion of BGC-823 cells treated with TROP-2 siRNA was decreased as compared with control group (P <0. 01 ). Conclusion TROP-2 gene might play an important role in adhesion, migration, and invasion of human gastric cancer cells, siRNA targeted TROP-2 could effectively inhibit adhesion, migration, and invasion of human gastric cancer cells. Key words: Gastric carcinoma; TROP-2; RNA interference; Invasion

Objective To investigate the expression of cell adhesion molecule 4 (CADM4) in gastric cancer tissues and cell lines as well as its effect on apoptosis, autophagy, invasion and metastasis of human gastric cancer cells BGC-823. Methods The expression of CADM4 in 60 cases of gastric cancer tissues and their adjacent tissues was detected by Real-time polymerase chain reaction (PCR). The relationship between CADM4 expression and clinicopathological features of gastric carcinoma was analyzed. The expression of CADM4 was detected in 7 strains of gastric cancer cells (HGC-27, BGC-823, MKN-45, MGC-803, SGC-7901, NCL-N87 and AGS) and the normal gastric mucosa cell line, GES-1, was used as the control. The gastric cancer cells with the lowest level of CADM4 were chosen for the transfection with lentivirus vector of overexpressing CADM4 (LV-CADM4). Real-time PCR was used to detect the expression of CADM4 mRNA in the transfected BGC-823 cells. Flow cytometry was used to detect the cell apoptosis ratio and mitochondrial trans-membrane potential. Transwell invasion assay and cell scratch assay were used to detect the migration and invasion of transfected BGC-823 cells. Western blotting was used to detect the expression of proteins associated with apoptosis, autophagy, invasion and metastasis. Results The relative expression of CADM4 in gastric carcinoma tissues was 0.29±0.03, lower than that (1.20±0.15) of the adjacent tissues (P=0.000). Its expression was related to TNM clinical stage, differentiation, depth of invasion and lymph node metastasis (all P=0.000). The expression level of CADM4 in BGC-823 cells was obviously lower than that in HGC-27, MKN-45, MGC-803, SGC-7901, NCL-N87, AGS and GES-1 cells (P=0.000). As compared with blank control group and negative virus control group, LV-CADM4 promoted the apoptosis of BGC-823 cells and greatly decreased the mitochondrial trans-membrane potential (all P=0.000); meanwhile the expression levels of B cell lymphoma/leukemia-2 (bcl-2), p62 and matrix metalloproteinase (MMP)-9 proteins were down-regulated, and the expression levels of bcl-2 associated X protein (bax), Caspase-9, microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 proteins were up-regulated (all P=0.000). Conclusion The expression of CADM4 was down-regulated in gastric cancer tissues and cells, and up-regulation of CADM4 can induce apoptosis and autophagy via the mitochondrial pathway in BGC-823 cells, and inhibit the invasion and metastasis in BGC-823 cells. Key words: Gastric cancer; Apoptosis; Autophagy; Invasion; Metastasis