title: Gab1 regulates proliferation and migration through the PI3K/Akt signaling pathway in intrahepatic cholangiocarcinoma.
abstract: Intrahepatic cholangiocarcinoma is the second most common primary malignant tumor of the liver, and it originates from the intrahepatic biliary duct epithelium. Prognosis is poor due to lack of effective comprehensive treatments. In this study, we assessed the expression of Gab1, VEGFR-2, and MMP-9 in intrahepatic cholangiocarcinoma solid tumors by immunohistochemistry and determined whether their expression was associated with clinical and pathological features. We found that expression of Gab1, VEGFR-2, and MMP-9 was highly and positively correlated with each other and with lymph node metastasis and TNM stage in intrahepatic cholangiocarcinoma tissues. Interference of Gab1 and VEGFR-2 expression via siRNA in the intrahepatic cholangiocarcinoma cell line RBE resulted in decreased PI3K/Akt pathway activity. Inhibition of Gab1 and VEGFR-2 expression also caused decreased cell proliferation, cell cycle arrested in G1 phase, increased apoptosis, and decreased invasion in RBE cells. These results suggest that Gab1, VEGFR-2, and MMP-9 contribute significantly to the highly malignant behavior of intrahepatic cholangiocarcinoma. The regulation of growth, apoptosis, and invasion by Gab1 through the VEGFR-2/Gab1/PI3K/Akt signaling pathway may represent potential targets for improving the treatment of intrahepatic cholangiocarcinoma.
authors.affiliation: Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People's Republic of China.
authors.forename: Haiquan
authors.initials: H
authors.lastname: Sang
authors.affiliation: Department of Clinical Genetics, Shengjing Hospital, China Medical University, Shenyang, 110004, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People's Republic of China.
authors.forename: Hangyu
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People's Republic of China. sanghaiquan0725@hotmail.com.
authors.forename: Jingang
authors.initials: J
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics*; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D051058:Oncogene Protein v-akt / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011379:Prognosis; D034741:RNA, Small Interfering; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C098587:GAB1 protein, human; D034741:RNA, Small Interfering; D019869:Phosphatidylinositol 3-Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2; D051058:Oncogene Protein v-akt; D020780:Matrix Metalloproteinase 9
keywords: Apoptosis; Gab1; Intrahepatic cholangiocarcinoma; Migration; PI3K/Akt; Proliferation