Tumour-promoting role of SOCS1 in colorectal cancer cells

Sci Rep. 2015 Sep 22:5:14301. doi: 10.1038/srep14301.

Abstract

The SOCS1 (Suppressor Of Cytokine Signalling 1) protein is considered a tumour suppressor. Notably, the SOCS1 gene is frequently silenced in cancer by hypermethylation of its promoter. Besides blocking inflammation, SOCS1 tumour suppressor activity involves Met receptor inhibition and enhancement of p53 tumour suppressor activity. However, the role of SOCS1 in colorectal cancer (CRC) remains understudied and controversial. Here, we investigated SOCS1 relevance for CRC by querying gene expression datasets of human CRC specimens from The Cancer Genome Atlas (TCGA), and by SOCS1 gain/loss-of-function analyses in murine and human colon carcinoma cells. Our results show that SOCS1 mRNA levels in tumours were more often elevated than reduced with respect to matched adjacent normal tissue of CRC specimens (n = 41). The analysis of TCGA dataset of 431 CRC patients revealed no correlation between SOCS1 expression and overall survival. Overexpression of SOCS1 in CRC cells triggered cell growth enhancement, anchorage-independent growth and resistance to death stimuli, whereas knockdown of SOCS1 reduced these oncogenic features. Moreover, SOCS1 overexpression in mouse CT26 cells increased tumourigenesis in vivo. Biochemical analyses showed that SOCS1 pro-oncogenic activity correlated with the down-modulation of STAT1 expression. Collectively, these results suggest that SOCS1 may work as an oncogene in CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Disease Models, Animal
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Interferon-gamma / metabolism
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • STAT1 Transcription Factor / metabolism
  • Signal Transduction
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics*
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation

Substances

  • RNA, Messenger
  • SOCS1 protein, human
  • STAT1 Transcription Factor
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Tumor Suppressor Protein p53
  • Hepatocyte Growth Factor
  • Interferon-gamma