IFITM1 promotes the metastasis of human colorectal cancer via CAV-1

Cancer Lett. 2015 Nov 1;368(1):135-143. doi: 10.1016/j.canlet.2015.07.034. Epub 2015 Aug 7.

Abstract

Interferon-induced transmembrane protein 1 (IFITM1) is one of the interferon-induced transmembrane protein family members. In this study, we reported that the elevated IFITM1 expression in human colorectal cancer (CRC) significantly correlated with CRC lymph node and distance metastasis as well as a more advanced clinical stage. Importantly, elevated IFITM1 expression is an independent prognostic factor for poor survival. To investigate the molecular mechanisms, we showed that over-expression of IFITM1 in CRC cells promoted, whereas knockdown of IFITM1 expression inhibited, cell migration/invasion and tumorigenicity in vitro. Furthermore, we identified Caveolin-1 (CAV1) as a downstream target of IFITM1-induced cell invasion, as knockdown of CAV1 abrogated siIFITM1 mediated inhibition of cell invasion in CRC cells. In addition, in a CRC cohort of 229 patients, the expression of IFITM1 inversely correlated with the expression of CAV1. These results suggested that IFITM1 promotes the aggressiveness of CRC cells, and it is a potential prognostic marker and therapeutic target for CRC.

Keywords: CAV1; Colorectal cancer; IFITM1; Metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism*
  • Caco-2 Cells
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism*
  • Cell Movement*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Proportional Hazards Models
  • RNA Interference
  • Signal Transduction
  • Time Factors
  • Transfection

Substances

  • Antigens, Differentiation
  • CAV1 protein, human
  • Caveolin 1
  • leu-13 antigen