IFITM1 promotes the metastasis of human colorectal cancer via CAV-1. Issue 1 (1st November 2015)

• Record Type: Journal Article
• Authors: Yu, Fang; Xie, Dan; Ng, Samuel S.; Lum, Ching Tung; Cai, Mu-Yan; Cheung, William K.; Kung, Hsiang-Fu; Lin, Guimiao; Wang, Xiaomei; Lin, Marie C.
• Is Part Of: Cancer letters. Volume 368:Issue 1(2016)
• Page Start: 135
• Page End: 143
• Publication Date: 2015-11-01
• Subjects: IFITM1 -- Colorectal cancer -- Metastasis -- CAV1; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2015.07.034
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: Elevated IFITM1 expression is important in the acquisition of an aggressive phenotype and poor prognostic in CRC. IFITM1 expression is an independent prognostic factor for CRC patient survival. IFITM1 could influence motility, invasion and tumorigenicity of CRC cells. IFITM1 negatively influences CAV1 expression, and CAV1 is at least partly responsible for IFITM1-induced cell invasion. IFITM1 is potentially a useful diagnostic and prognostic marker as well as a therapeutic target for CRC patients. 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.