Biochemical and Biophysical Research Communications, Vol.470, No.2, 397-404, 2016
Rab11-FIP2 promotes colorectal cancer migration and invasion by regulating PI3K/AKT/MMP7 signaling pathway
Rab11-family interacting proteins (Rab11-FIPs) belong to an evolutionarily conserved protein family and act as effector molecules for the Rab11 family of small GTPases. Recent evidence suggests that Rab11-FIPs have important roles in tumor progression and metastasis. However, the contribution of Rab11-FIPs to colorectal carcinoma (CRC) remains elusive. Our study focuses on elucidating the role of Rab11-FIP2 in the migration and invasion of colorectal cancer cells. We firstly found upregulation of Rab11-FIP2 in CRC tissues compared with peritumor tissues by oncomine data-mining analysis, western blot analysis and immunohistochemistry (IHC) analysis, respectively. Then, we demonstrated that knockdown of Rab11-FIP2 via siRNAs transfection resulted in a decrease in migration and invasion of CRC cells, while over expression of Rab11-FIP2 via lentiviral infection increased migration and invasion of CRC cells. In addition, we verified that Rab11-FIP2 promoted migration and invasion of CRC cells through upregulating MMP7 expression. Finally, using several kinase inhibitors, our results showed that Rab11-FIP2 regulated MMP7 expression through activating PI3K/Akt signaling. Our data suggested a potential role of Rab11-FIP2 in tumor progression and provided novel insights into the mechanism of how Rab11-FIP2 positively regulated cell migration and invasion in CRC cells. (C) 2016 Elsevier Inc. All rights reserved.