Abstract
Hilar cholangiocarcinoma is a highly aggressive malignancy originating from the hilar biliary duct epithelium. Due to few effective comprehensive treatments, the prognosis of hilar cholangiocarcinoma is poor. In this study, immunohistochemistry was first used to detect and analyze the expression of Gab1, VEGFR-2, and MMP-9 in hilar cholangiocarcinoma solid tumors and the relationships to the clinical pathological features. Furthermore, Gab1 and VEGFR-2 siRNA were used to interfere the hilar cholangiocarcinoma cell line ICBD-1 and then detect the PI3K/Akt signaling pathway, MMP-9 levels and malignant biological behaviors of tumor cells. The data showed that 1. Gab1, VEGFR-2, and MMP-9 were highly expressed and positively correlated with each other in hilar cholangiocarcinoma tissues, which were related to lymph node metastasis and differentiation. 2. After Gab1 or VEGFR-2 siRNA interference, PI3K/Akt pathway activity and MMP-9 levels were decreased in ICBD-1 cells. At the same time, cell proliferation decreased, cell cycle arrested in G1 phase, apoptosis increased and invasion decreased. These results suggest that the expression of Gab1, VEGFR-2, and MMP-9 are significantly related to the malignant biological behavior of hilar cholangiocarcinoma. Gab1 regulates growth, apoptosis and invasion through the VEGFR-2/Gab1/PI3K/Akt signaling pathway in hilar cholangiocarcinoma cells and influences the invasion of tumor cells via MMP-9.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing / deficiency*
-
Adaptor Proteins, Signal Transducing / genetics*
-
Adaptor Proteins, Signal Transducing / metabolism
-
Bile Duct Neoplasms / genetics
-
Bile Duct Neoplasms / pathology*
-
Bile Ducts, Intrahepatic / pathology*
-
Cell Line, Tumor
-
Cell Movement / genetics
-
Cell Proliferation
-
Cholangiocarcinoma / genetics
-
Cholangiocarcinoma / pathology*
-
Down-Regulation / genetics*
-
G1 Phase Cell Cycle Checkpoints / genetics
-
Gene Expression Regulation, Neoplastic
-
Humans
-
Matrix Metalloproteinase 9 / genetics
-
Matrix Metalloproteinase 9 / metabolism
-
Phosphatidylinositol 3-Kinases / metabolism
-
Proto-Oncogene Proteins c-akt / metabolism
-
RNA Interference*
-
RNA, Small Interfering / genetics
-
Signal Transduction / genetics
-
Vascular Endothelial Growth Factor Receptor-2 / deficiency
-
Vascular Endothelial Growth Factor Receptor-2 / genetics
-
Vascular Endothelial Growth Factor Receptor-2 / metabolism
Substances
-
Adaptor Proteins, Signal Transducing
-
GAB1 protein, human
-
RNA, Small Interfering
-
Phosphatidylinositol 3-Kinases
-
Vascular Endothelial Growth Factor Receptor-2
-
Proto-Oncogene Proteins c-akt
-
Matrix Metalloproteinase 9
Grants and funding
This work was supported by grants from the National Natural Science Foundation of China (project no. 81001091) to Tingting Li. The funder had a role in study design, data analysis, decision to publish, and preparation of the manuscript.