Frequent amplification of PTP1B is associated with poor survival of gastric cancer patients

The protein tyrosine phosphatase 1B (PTP1B), a non-transmembrane protein tyrosine phosphatase, has been implicated in gastric pathogenesis. Several lines of recent evidences have shown that PTP1B is highly amplified in breast and prostate cancers. The aim of this study was to investigate PTP1B amplification in gastric cancer and its association with poor prognosis of gastric cancer patients, and further determine the role of PTP1B in gastric tumorigenesis. Our data demonstrated that PTP1B was significantly up-regulated in gastric cancer tissues as compared with matched normal gastric tissues by using quantitative RT-PCR (qRT-PCR) assay. In addition, copy number analysis showed that PTP1B was amplified in 68/131 (51.9%) gastric cancer cases, whereas no amplification was found in the control subjects. Notably, PTP1B amplification was positively associated with its protein expression, and was significantly related to poor survival of gastric cancer patients. Knocking down PTP1B expression in gastric cancer cells significantly inhibited cell proliferation, colony formation, migration and invasion, and induced cell cycle arrested and apoptosis. Mechanically, PTP1B promotes gastric cancer cell proliferation, survival and invasiveness through modulating Src-related signaling pathways, such as Src/Ras/MAPK and Src/phosphatidylinositol-3-kinase (PI3K)/Akt pathways. Collectively, our data demonstrated frequent overexpression and amplification PTP1B in gastric cancer, and further determined the oncogenic role of PTP1B in gastric carcinogenesis. Importantly, PTP1B amplification predicts poor survival of gastric cancer patients.     

Expression of apurinic/apyrimidinic endonuclease-1 (APE-1) in H. pylori-associated gastritis, gastric adenoma, and gastric cancer

Background and Aim: Apurinic/apyrimidinic endonuclease‐1 (APE‐1) is a key enzyme in DNA base excision repair (BER), linked to cancer chemosensitivity. However, little is known about the localization of APE‐1 in Helicobacter pylori‐infected gastric mucosa or its role in the development of gastric cancer. To investigate the role of APE‐1 in the development of gastric cancer, we examined APE‐1 expression and localization in cultured cells and gastric biopsies from patients with H. pylori‐infected gastritis or gastric adenoma, and from surgically resected gastric cancer. Methods: APE‐1 mRNA and protein expression were determined in H. pylori (CagA+) water‐extract protein (HPWEP)‐stimulated MKN‐28 cells, gastric adenocarcinoma cell‐line (AGS) cells, and human peripheral macrophages by real‐time polymerase chain reaction and Western blot analysis. APE‐1 expression and 8‐OHdG as a measure of oxidative DNA damage were evaluated by immunostaining. Localization of APE‐1 and IκBα phosphorylation in gastric adenoma and gastric cancer tissues were evaluated by single‐ and double‐label immunohistochemistry. Results: In studies in vitro, HPWEP‐stimulation significantly increased APE‐1 mRNA expression levels in both MKN‐28 cells and human peripheral macrophages. Hypo/reoxygenation treatment significantly increased APE‐1 protein expression in HPWEP‐stimulated MKN‐28 cells. HPWEP stimulation significantly increased both APE‐1 expression and IκBα phosphorylation levels in MKN‐28 and AGS cells. In human tissues, APE‐1 expression in H. pylori‐infected gastritis without goblet cell metaplasia was significantly increased as compared to that in tissues from uninfected subjects. Eradication therapy significantly reduced both APE‐1 and 8‐OHdG expression levels in the gastric mucosa. APE‐1 expression was mainly localized in epithelial cells within gastric adenoma and in mesenchymal cells of gastric cancer tissues. APE‐1 expression in gastric cancer tissues was significantly reduced compared to that in H. pylori‐infected gastric adenoma, while 8‐OHdG index and IκBα phosphorylation levels did not differ between these two neoplastic tissue types. Co‐localization of APE‐1 and IκBα phosphorylation was observed not in gastric cancer cells but in gastric adenoma cells. Conclusion: H. pylori infection is associated with increased APE‐1 expression in human cell lines and in gastric tissues from subjects with gastritis and gastric adenomas. The observed distinct expression patterns of APE‐1 and 8‐OHdG in gastric adenoma and gastric cancer tissues may provide insight into the progression of these conditions and warrants further investigation.     

PTP4A3 (PRL-3) expression correlate with lymphatic metastases in gastric cancer

Many studies have proved that protein tyrosine phosphatase type IVAmember 3 (PTP4A3, PRL-3) plays a major role in the metastasis of gastric cancer, especially to local lymph nodes. The objective of the current study was to assess the expression of PTP4A3 in gastric cancer in correlation with chosen anatomoclinical parameters and patients' survival. Atotal of 71 patients with gastric carcinomas were divided according to Lauren's, Goseki's, Bormann's and Kubo's classifications. The level of PTP4A3 was determined immunohistochemically using a mouse monoclonal anti-PTP4A3 antibody (clone 3B6, anti-human PTP4A3, Attogen Biomedical Research, USA). A statistically significant correlation was observed between PTP4A3 and Kubo's classifications (p=0.0454) and on the verge of statistical significance with Lauren's classification (p=0.0503). The expression of the protein was associated more with the poorly-differentiated mucoid carcinoma and diffused-type carcinoma (58% of cases). We demonstrated a statistically significant correlation between local lymph node involvement and positive expression of PTP4A3 in the primary tumour (p=0.0000). The current study seems to prove that PTP4A3 may have a significant impact on the lymphatic spread of gastric carcinoma. The protein expression is also significantly associated with gastric carcinomas having a worse prognosis, although patients' survival rate showed lack of correlation with PTP4A3 expression.     

Low‐dose taxotere enhances the ability of sorafenib to induce apoptosis in gastric cancer models

Despite the low efficacy of conventional antitumour drugs, chemotherapy remains an essential tool in controlling advanced gastric and oesophageal cancers. We aimed to provide a biological rationale based on the sorafenib–taxotere interaction for the clinical treatment of gastric cancer. In vitro experiments were performed on four human gastric cancer cell lines (GK2, AKG, KKP and NCI‐N87). Cytotoxicity was evaluated by sulforhodamine B (SRB) assay, cell cycle perturbations, apoptosis and mitotic catastrophe were assessed by flow cytometric and microscopic analyses, and protein expression was studied by Western blot. In the in vivo experiments, nude mice xenografted with the most resistant line were treated with sorafenib and docetaxel singly or in association. Sorafenib inhibited cell growth (IG50 values ranged from 3.4 to 8.1 μM) and caused down‐regulation of MAP‐K/ERK phosphorylation and of mcl‐1 and p‐bad expression after a 48‐hr exposure. Apoptosis induction was associated with caspase‐3 and ‐9 activation and mitochondrial membrane depolarization. The drug combination enhanced apoptosis (up to 80%) and produced a synergistic interaction when low doses of the taxane preceded administration of the antityrosine kinase. This synergism was probably due to the induction of an anomalous multidiploid G0‐G1 peak and to consequent mitotic catastrophe, which increased sensitivity to sorafenib. Consistent with in vitro results, the docetaxel–sorafenib sequence exhibited high therapeutic efficacy in NCI‐N87 mouse xenografts producing tumour weight inhibition (> 65%), tumour growth delay (up to 25 days) and increased mouse survival (30%). Our findings suggest the potential clinical usefulness of treatment with sorafenib and docetaxel for advanced gastric cancer.     

Protein tyrosine phosphatase-1B and T-cell protein tyrosine phosphatase regulate IGF-2-induced MCF-7 cell migration

The protein tyrosine phosphatase-1B (PTP1B) and the T-cell protein tyrosine phosphatase (TC-PTP) have been implicated in down-regulation of tyrosine kinase receptors, conferring anti-oncogenic functions to these PTPases. However, recent work has shown that PTP1B is positively implicated in oncogenic properties of breast cancer cells by regulating the ERK pathway. Here, we studied the function of PTP1B and TC-PTP in IGF-2-induced growth, survival and migration of MCF-7 breast cancer cells. Using siRNA, we showed that reduction in the expression of these PTPases decreased cell growth and ERK phosphorylation. Reduction in the expression of these PTPases did not impair IGF-2 effects on cell survival to acute treatment with 4-OH Tamoxifen. In contrast, IGF-2-induced MCF-7 cell migration was markedly impaired by reduction of PTP1B or TC-PTP expression, independently of the ERK pathway. This novel finding reinforces the potential role of these PTPases as therapeutic targets for treatment of breast cancer.     

两歧双歧杆菌胞外多糖对胃癌细胞及hTERT的影响

【目的】研究从双歧杆菌属两歧双歧杆菌(Bifidobacterium bifidum)提取的细胞表面成分胞外多糖(Exopolysaccharide, B.EPS)对人胃癌细胞BGC-823的生长抑制作用及对端粒酶限速因子hTERT活性的影响。【方法】将三种不同浓度B.EPS体外作用于胃癌细胞BGC823,MTT法检测细胞生长抑制率并辅以形态学观察;异硫氰酸盐(FITC)联合PI染色,通过流式细胞术检测肿瘤细胞初期调亡情况;肿瘤细胞端粒酶限速因子hTERT mRNA经RT-PCR检测B.EPS对端粒酶活性抑制作用;通过荧光分光光度计显示B.EPS 对胃癌细胞作用后胞内Ca2+含量变化。【结果】经过检测发现,B.EPS对人胃癌细胞BGC823的生长显著抑制(P＜0.05)呈剂量时间反应关系;细胞中hTERT mRNA在B.EPS的作用下表达降低(P＜0.05),有一定剂量效应关系;随着B.EPS对肿瘤细胞的抑制,细胞内Ca2+含量显著增加(P＜0.05)。【结论】B.EPS诱导人胃癌细胞BGC823调亡的机制可能与改变肿瘤细胞端粒酶限速因子hTERT mRNA表达量和细胞内钙离子浓度有关。     

Overexpression of PTP1B in human colorectal cancer and its association with tumor progression and prognosis

Protein tyrosine phosphatase 1B (PTP1B) is a non-transmembrane protein tyrosine phosphatase that has been implicated in cancer pathogenesis. However, the expression level and the role of PTP1B in the development and prognosis of colorectal cancer (CRC) remain unclear. In this study, the expression of PTP1B in CRC tissues and matched noncancerous tissues were detected by using immunohistochemistry, real-time PCR and Western blotting. The correlations between PTP1B expression level and clinicopathologic characteristics and patient survival were analyzed. We found that PTP1B expression was significantly higher in CRC tissues compared with matched non-tumour tissues. Statistical analysis showed that the PTP1B expression was correlated with tumor differentiation, tumor invasion, lymph node metastasis, and TNM stage. Patients with higher expressions of PTP1B had the lower survival (P = 0.012). Taken together, our results suggest that PTP1B expression might play a critical role in the progression of CRC and may serve as a valuable prognostic biomarker for CRC.     

Redox regulation of the protein tyrosine phosphatase PTP1B in cancer cells

The oxidation and inactivation of protein tyrosine phosphatases is one mechanism by which reactive oxygen species influence tyrosine phosphorylation-dependent signaling events and exert their biological functions. In the present study, we determined the redox status of endogenous protein tyrosine phosphatases in HepG2 and A431 human cancer cells, in which reactive oxygen species are produced constitutively. We used mass spectrometry to assess the state of oxidation of the catalytic cysteine residue of endogenous PTP1B and show that this residue underwent both reversible and irreversible oxidation to high stoichiometry in response to intrinsic reactive oxygen species production. In addition, our data show that the oxidation of PTP1B is specific to the active site Cys, with the other Cys residues in the protein remaining in a reduced state. Treatment of these cells with diphenyleniodonium, an inhibitor of NADPH oxidases, decreased reactive oxygen species levels. This resulted in inhibition of protein tyrosine phosphatase oxidation, concomitant with decreased tyrosine phosphorylation of cellular proteins and inhibition of anchorage-independent cell growth. Therefore, our data also suggest that the high level of intrinsic reactive oxygen species may contribute to the transformed phenotype of HepG2 and A431 cells via constitutive inactivation of cellular protein tyrosine phosphatases.     

视黄酸对胃癌细胞周期的调控

Retinoic acid can induce growth inhibition and apoptosis, and regulate cell cycle in many types of cancer cell lines. In this study, we investigated the role of all-trans retinoic acid (ATRA) and its mechanism of action in human gastric cancer cell lines. Our results demonstrated that ATRA effectively inhibited growth in three of four gastric cancer cell lines by induction of G0/G1 arrest, and did not induce apoptosis in four gastric cancer cell lines. In RA-sensitive cell lines, ATRA-induced G0/G1 arrest is associated with down regulaton of c-myc and hyperphosphorylated Rb expression, and up regulation of p21WAF1/CIP1 and p53 expression. There were no significant changes in cyclin D1 or CDK4 expression induced by ATRA. Futhermore, expression of these genes were not regulated by ATRA in ATRA-resistant gastric cancer cell line. These results indicate that growth inhibition, rather than apoptosis, is correlated with G0/G1 arrest of these cell lines, more important molecules related cell cycle, including c-myc, p21WAF1/CIP1, p53 and Rb, are involveed in regulation of cell cycle in gastric cancer cells.     

Human ribosomal protein S13 promotes gastric cancer growth through down‐regulating p27Kip1

Our previous works revealed that human ribosomal protein S13 (RPS13) was up‐regulated in multidrug‐resistant gastric cancer cells and overexpression of RPS13 could protect gastric cancer cells from drug‐induced apoptosis. The present study was designed to explore the role of RPS13 in tumorigenesis and development of gastric cancer. The expression of RPS13 in gastric cancer tissues and normal gastric mucosa was evaluated by immunohistochemical staining and Western blot analysis. It was found RPS13 was expressed at a higher level in gastric cancer tissues than that in normal gastric mucosa. RPS13 was then genetically overexpressed in gastric cancer cells or knocked down by RNA interference. It was demonstrated that up‐regulation of RPS13 accelerated the growth, enhanced in vitro colony forming and soft agar cologenic ability and promoted in vivo tumour formation potential of gastric cancer cells. Meanwhile, down‐regulation of RPS13 in gastric cancer cells resulted in complete opposite effects. Moreover, overexpression of RPS13 could promote G1 to S phase transition whereas knocking down of RPS13 led to G1 arrest of gastric cancer cells. It was further demonstrated that RPS13 down‐regulated p27^kip1 expression and CDK2 kinase activity but did not change the expression of cyclin D, cyclin E, CDK2, CDK4 and p16^INK4A. Taken together, these data indicate that RPS13 could promote the growth and cell cycle progression of gastric cancer cells at least through inhibiting p27^kip1 expression.     

Enolase1 overexpression regulates the growth of gastric cancer cells and predicts poor survival

Gastric cancer has become the third most common cancer around the world. In patients with gastric cancer, the 5-year survival rate is still low. However, the mechanism underlying gastric cancer remains largely unknown. As a glycolytic enzyme, enolase 1 (ENO1) is widely expressed in most tissues. The functions of ENO1 have been reported in various types of cancer. Here in this study, we identified that ENO1 promoted the growth of gastric cancer cells through diverse mechanisms. Our immunohistochemical, bioinformatic and Western blot data showed that ENO1 was significantly overexpressed in human gastric cancer cell lines and tissues. The survival analysis revealed that ENO1 overexpression predicted poor survival in the patients suffering gastric cancer. Knockdown of ENO1 expression repressed the rate of proliferation and capacity of colony formation in two human gastric cancer cell lines (MGC-803 and MKN-45). In addition, knockdown of the expression of ENO1 led to the arrest of the cell cycle at the G1 phase and promoted the apoptosis of MKN-45 and MGC-803 cells. The further microarray and bioinformatic analysis revealed that ENO1 regulated the expression of diverse genes, many of which are involved in the progress of cancer. Taken together, our data demonstrated that ENO1 was an oncogene-like factor and might serve as a promising target for the treatment of human gastric cancer.     

Changes in protein tyrosine phosphatase type IVA member 1 and zinc finger protein 36 C3H type-like 1 expression demonstrate altered estrogen and progestin effect in medroxyprogesterone acetate-resistant and estrogen-independent breast cancer cell models

Estrogen stimulates proliferation in hormone-responsive breast cancer cells. Progestins inhibit the estrogen-mediated growth in these cells and are used in the treatment of mammary carcinomas. We applied cDNA microarray and real-time RT-PCR methods to reveal 17β-estradiol- and medroxyprogesterone acetate (MPA)-regulated genes in MCF-7 breast cancer cells. We identified six genes, two of which were novel MPA and/or 17β-estradiol-regulated genes: protein tyrosine phosphatase type IVA, member 1 (PTP4A1) and zinc finger protein 36, C3H type-like 1 (ZFP36L1). PTP4A1 expression was upregulated by 17β-estradiol and this was opposed by MPA treatment of the cells. ZFP36L1 proved to be a direct target of MPA. Since MPA has also been shown to bind to glucocorticoid- and androgen receptors, we studied the regulation of the genes with progesterone, synthetic progestin R5020, dexamethasone and dihydrotestosterone. We also assessed the expression and hormonal regulation of PTP4A1 and ZFP36L1 mRNA in MCF-7-derived MPA-resistant and estrogen-independent sublines. The regulation of PTP4A1 expression upon 17β-estradiol and combined 17β-estradiol and MPA treatment was completely reversed in the estrogen-independent and MPA-resistant sublines, respectively. This study suggests an important role for PTP4A1 in cell growth, and shows that MPA may potentiate the effect of 17β-estradiol in the MPA-resistant breast cancer cells.     

Lysophosphatidic acid modulates the association of PTP1B with N‐cadherin/catenin complex in SKOV3 ovarian cancer cells

LPA (lysophosphatidic acid) is a natural phospholipid that plays important roles in promoting cancer cell proliferation, invasion and metastases. We previously reported that LPA induces ovarian cancer cell dispersal and disruption of AJ (adherens junction) through the activation of SFK (Src family kinases). In this study, we have investigated the regulatory mechanisms during the early phase of LPA‐induced cell dispersal. An in vitro model of the ovarian cancer cell line SKOV3 for cell dispersal was used. LPA induces rapid AJ disruption by increasing the internalization of N‐cadherin‐β‐catenin. By using immunoprecipitations, LPA was shown to induce increased tyrosine phosphorylation of β‐catenin and alter the balance of β‐catenin‐bound SFK and PTP1B (phosphotyrosine phosphatase 1B). The altered balance of tyrosine kinase/phosphatase correlated with a concomitant disintegration of the β‐catenin‐α‐catenin, but not the β‐catenin—N‐cadherin complex. This disintegration of β‐catenin from α‐catenin and the cell dispersal caused by LPA can be rescued by blocking SFK activity with the chemical inhibitor, PP2. More importantly, PP2 also restores the level of PTP1B bound to β‐catenin. We propose that LPA signalling alters AJ stability by changing the dynamics of tyrosine kinase/phosphatase bound to AJ proteins. This work provides further understanding of the early signalling events regulating ovarian cancer cell dispersal and AJ disruption induced by LPA.     

Phosphorylation and activation of protein tyrosine phosphatase (PTP) 1B by insulin receptor

We have previously reported a direct in vivo interaction between the activated insulin receptor and protein-tyrosine phosphatase-1B (PTP1B), which leads to an increase in PTP1B tyrosine phosphorylation. In order to determine if PTP1B is a substrate for the insulin receptor tyrosine kinase, the phosphorylation of the Cys 215 Ser, catalytically inactive mutant PTP1B (CS-PTP1B) was measured in the presence of partially purified and activated insulin receptor. In vitro, the insulin receptor tyrosine kinase catalyzed the tyrosine phosphorylation of PTP1B. 53% of the total cellular PTP1B became tyrosine phosphorylated in response to insulin in vivo. Tyrosine phosphorylation of PTP1B by the insulin receptor was absolutely dependent upon insulin-stimulated receptor autophosphorylation and required an intact kinase domain, containing insulin receptor tyrosines 1146, 1150 and 1151. Tyrosine phosphorylation of wild type PTP1B by the insulin receptor kinase increased phosphatase activity of the protein. Intermolecular transdephosphorylation was demonstrated both in vitro and in vivo, by dephosphorylation of phosphorylated CS-PTP1B by the active wild type enzyme either in a cell-free system or via expression of the wild type PTP1B into Hirc-M cell line, which constitutively overexpress the human insulin receptor and CS-PTP1B. These results suggest that PTP1B is a target protein for the insulin receptor tyrosine kinase and PTP1B can regulate its own phosphatase activity by maintaining the balance between its phosphorylated (the active form) and dephosphorylated (the inactive form) state.     

Inhibition of protein-tyrosine phosphatase 1B (PTP1B) mediates ubiquitination and degradation of Bcr-Abl protein

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized at the molecular level by the expression of Bcr-Abl, a chimeric protein with deregulated tyrosine kinase activity. The protein-tyrosine phosphatase 1B (PTP1B) is up-regulated in Bcr-Abl-expressing cells, suggesting a regulatory link between the two proteins. To investigate the interplay between these two proteins, we inhibited the activity of PTP1B in Bcr-Abl-expressing TonB.210 cells by either pharmacological or siRNA means and examined the effects of such inhibition on Bcr-Abl expression and function. Herein we describe a novel mechanism by which the phosphatase activity of PTP1B is required for Bcr-Abl protein stability. Inhibition of PTP1B elicits tyrosine phosphorylation of Bcr-Abl that triggers the degradation of Bcr-Abl through ubiquitination via the lysosomal pathway. The degradation of Bcr-Abl consequently inhibits tyrosine phosphorylation of Bcr-Abl substrates and the downstream production of intracellular reactive oxygen species. Furthermore, PTP1B inhibition reduces cell viability and the IC(50) of the Bcr-Abl inhibitor imatinib mesylate. Degradation of Bcr-Abl via PTP1B inhibition is also observed in human CML cell lines K562 and LAMA-84. These results suggest that inhibition of PTP1B may be a useful strategy to explore in the development of novel therapeutic agents for the treatment of CML, particularly because host drugs currently used in CML such as imatinib focus on inhibiting the kinase activity of Bcr-Abl.     

Gene expression signature analysis identifies vorinostat as a candidate therapy for gastric cancer

Background

Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future.

Methodology/Principal Findings

Using microarray technology, we generated a gene expression profile of human gastric cancer–specific genes from human gastric cancer tissue samples. We used this profile in the Broad Institute''s Connectivity Map analysis to identify candidate therapeutic compounds for gastric cancer. We found the histone deacetylase inhibitor vorinostat as the lead compound and thus a potential therapeutic drug for gastric cancer. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines. Pharmacological and genetic inhibition of autophagy however, increased the therapeutic efficacy of vorinostat, indicating that a combination of vorinostat with autophagy inhibitors may therapeutically be more beneficial. Moreover, gene expression analysis of gastric cancer identified a collection of genes (ITGB5, TYMS, MYB, APOC1, CBX5, PLA2G2A, and KIF20A) whose expression was elevated in gastric tumor tissue and downregulated more than 2-fold by vorinostat treatment in gastric cancer cell lines. In contrast, SCGB2A1, TCN1, CFD, APLP1, and NQO1 manifested a reversed pattern.

Conclusions/Significance

We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment.     

URG11 promotes gastric cancer growth and invasion by activation of β‐catenin signalling pathway

Upregulated gene 11 (URG11), a new gene upregulated by Heptatitis B Virus X protein (HBx), was previously shown to activate β‐catenin and promote hepatocellular growth and tumourigenesis. Although the oncogenic role of URG11 in the development of hepatocellular carcinoma has been well documented, its relevance to other human malignancies and the underlying molecular mechanisms remain largely unknown. Here we reported a novel function of URG11 to promote gastric cancer growth and metastasis. URG11 was found to be highly expressed in gastric cancer tissues compared with adjacent nontumourous ones by immunohistochemical staining and western blot. Knockdown of URG11 expression by small interfering RNA (siRNA) effectively attenuated the proliferation, anchorage‐independent growth, invasiveness and metastatic potential of gastric cancer cells. URG11 inhibition led to decreased expression of β‐catenin and its nuclear accumulation in gastric cancer cells and extensive costaining between URG11 and β‐catenin was observed in gastric cancer tissues. Transient transfection assays with the β‐catenin promoter showed that it was inhibited by URG11‐specific small inhibitory RNA. Moreover, suppression of endogenous URG11 expression results in decreased activation of β‐catenin/TCF and its downstream effector genes, cyclinD1 and membrane type 1 matrix metallopeptidase (MT1‐MMP), which are known to be involved in cell proliferation and invasion, respectively. Taken together, our data suggest that URG11 contributes to gastric cancer growth and metastasis at least partially through activation of β‐catenin signalling pathway. These findings also propose a promising target for gene therapy in gastric cancer.