A non-secretory form of FAM3B promotes invasion and metastasis of human colon cancer cells by upregulating Slug expression

Cancer Lett. 2013 Jan 28;328(2):278-84. doi: 10.1016/j.canlet.2012.09.026. Epub 2012 Oct 8.

Abstract

FAM3B mRNA has been predicted to have multiple splicing forms. Its secretory form PANDER is decreased in gastric cancers with high invasiveness and metastasis. Here we found that its non-secretory form FAM3B-258 was highly expressed in most colon cancer cell lines and colorectal adenocarcinoma tissues but not hepatocellular carcinoma, lung carcinoma and pancreatic adenocarcinoma cell lines. Elevation of FAM3B-258 was associated with poor cancer cell differentiation. Stable overexpression of FAM3B-258 in colon cancer cells downregulated adhesion proteins, upregulated Slug and Cdc42, promoted cell migration and invasion in vitro and metastasis in nude mice. Slug mediated FAM3B-258-induced downregulation of adhesion molecules, upregulation of Cdc42, and invasion of colon cancer cells. The expression of FAM3B-258 in human colorectal adenocarcinomas was positively correlated with Slug. These results suggest that FAM3B-258 promotes colon cancer cell invasion and metastasis through upregulation of Slug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Cytokines / genetics*
  • Cytokines / metabolism*
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis / genetics
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • RNA Isoforms / genetics
  • Snail Family Transcription Factors
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Cell Adhesion Molecules
  • Cytokines
  • FAM3B protein, human
  • Neoplasm Proteins
  • RNA Isoforms
  • SNAI1 protein, human
  • Snai2 protein, mouse
  • Snail Family Transcription Factors
  • Transcription Factors