title: IGFBP3, a transcriptional target of homeobox D10, is correlated with the prognosis of gastric cancer.
abstract: Homeobox D10 (HoxD10) plays important roles in the differentiation of embryonic cells and progression of breast cancer. Our previous report revealed that insulin-like growth factor binding protein-3 (IGFBP3) was regulated by HoxD10 in gastric cancer cells; however, the functional roles and underlying mechanisms of IGFBP3 in gastric cancer remain unclear. Here, we found that the expression of IGFBP3 were upregulated after ectopic expression of HoxD10 in gastric cancer cells. Chromatin immunoprecipitation assay showed that HoxD10 bound to three potential regions of IGFBP3 promoter. Exogenous HoxD10 significantly enhanced the activity of luciferase reporter containing these binding regions in gastric cancer cells. Further data showed that all of these binding sites had Hox binding element "TTAT". Immunohistochemical staining results revealed that IGFBP3 expression was significantly downregulated in 86 gastric adenocarcinomas tissues relative to their adjacent non-cancerous tissues (p<0.001). Moreover, IGFBP3 expression was significantly lower in gastric tumor with lymph node metastasis compared with that without lymph node metastasis (p=0.045). Patients with high expression level of IGFBP3 showed favorable 5 year overall survival (p=0.011). Knockdown of IGFBP3 accelerated gastric cancer cell migration and invasion and induced the expression of invasive factors including MMP14, uPA and uPAR. Thus, our data suggest that HoxD10-targeted gene IGFBP3 may suppress gastric cancer cell invasion and favors the survival of gastric cancer patients.
authors.affiliation: Department of Gastroenterology, Sir Runrun Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China ; Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xue
authors.affiliation: Department of Gastroenterology, Sir Runrun Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China ; Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China ; Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Guoming
authors.initials: G
authors.lastname: Sun
authors.affiliation: Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhuo
authors.affiliation: Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China ; Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Gastroenterology, Sir Runrun Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China ; Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Cuijuan
authors.initials: C
authors.lastname: Qian
authors.affiliation: Department of Gastroenterology, Sir Runrun Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China ; Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China ; Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Liangjing
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Sir Runrun Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China ; Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Si
authors.affiliation: Department of Gastroenterology, Sir Runrun Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China ; Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics*; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D055293:Receptors, Urokinase Plasminogen Activator; D014157:Transcription Factors; C072064:HOXD10 protein, human; D014568:Urokinase-Type Plasminogen Activator; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14