Rab11-FIP2 promotes colorectal cancer migration and invasion by regulating PI3K/AKT/MMP7 signaling pathway

Biochem Biophys Res Commun. 2016 Feb 5;470(2):397-404. doi: 10.1016/j.bbrc.2016.01.031. Epub 2016 Jan 11.

Abstract

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 overexpression 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.

Keywords: Colorectal carcinoma; Invasion; MMP7; Migration; Rab11-FIP2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Matrix Metalloproteinase 7 / metabolism*
  • Membrane Proteins / metabolism*
  • Neoplasm Invasiveness
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction
  • rab GTP-Binding Proteins

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Proto-Oncogene Proteins c-akt
  • MMP7 protein, human
  • Matrix Metalloproteinase 7
  • RAB11FIP2 protein, human
  • rab GTP-Binding Proteins