URG11 promotes gastric cancer growth and invasion by activation of beta-catenin signalling pathway.
Upregulated gene 11 (URG11), a new gene upregulated by Hepatitis B Virus X protein (HBx), was previously shown to activate beta-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 beta-catenin and its nuclear accumulation in gastric cancer cells and extensive costaining between URG11 and beta-catenin was observed in gastric cancer tissues. Transient transfection assays with the beta-catenin promoter showed that it was inhibited by URG11-specific small inhibitory RNA. Moreover, suppression of endogenous URG11 expression results in decreased activation of beta-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 beta-catenin signalling pathway. These findings also propose a promising target for gene therapy in gastric cancer.
State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, PR China.
Rui
R
Du
Lin
L
Xia
Shiren
S
Sun
Zhaorui
Z
Lian
Xue
X
Zou
Juan
J
Gao
Huahong
H
Xie
Rui
R
Fan
Jiugang
J
Song
Xiaohua
X
Li
Jie
J
Liu
Daiming
D
Fan
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002448:Cell Adhesion; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D015534:Trans-Activators; C547681:VWCE protein, human; D051176:beta Catenin