β1 integrin mediates colorectal cancer cell proliferation and migration through regulation of the Hedgehog pathway.
β1 integrin (ITGB1) is the major expressed integrin protein of normal cells and tumor-associated cells. It is often up-regulated in human malignancies and is involved in many developmental processes, such as tumor progression and metastasis. However, little is known about the function of ITGB1 in colorectal cancer. We constructed lentiviral vectors expressing ITGB1 or ITGB1-specific RNA interference (RNAi) and an unrelated control vector. After infecting HT29 cells in vitro, proliferation and migration were evaluated by Cell Counting Kit 8 (CCK-8) assays, transwell invasion assays, and Western blots. The influence of lentivirus infection on the tumor development capacity of HT29 cells in vivo was examined by xenografting the tumor cells. The expression of ITGB1 in the xenografted tumor cells was analyzed by immunohistochemistry. The up-regulation of ITGB1 significantly increased the proliferation in HT29 cells in vitro. Moreover, we found that the overexpression of ITGB1 up-regulated sonic hedgehog (Shh) while down-regulating Gli1 and SuFu in HT29-ITGB1 cells compared to controls. Moreover, the levels of c-myc and cyclin D1 proteins were up-regulated. Transwell assays showed that the number of migrating HT29-RNAi cells was lower than that in the other cell groups, indicating that ITGB1 significantly enhances the invasive ability of HT29 cells. In addition to these in vitro results, ITGB1 was found to be a significantly effective growth factor in a xenografted tumor mouse model. These results suggest that ITGB1 induces growth and invasion in a human colorectal cancer cell line through the hedgehog (Hh) signaling pathway in vitro and in vivo.
Department of Gastroenterology, Renmin Hospital of Wuhan University, 99 Zhi-Dong Zhang Road, Wuhan, 430060, Hubei Province, People's Republic of China.
Jia
J
Song
Jixiang
J
Zhang
Jing
J
Wang
Jun
J
Wang
Xufeng
X
Guo
Weiguo
W
Dong
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034622:RNA Interference; D015398:Signal Transduction; D015854:Up-Regulation
D053823:Hedgehog Proteins; D039641:Integrin beta Chains; D019938:Cyclin D1