MUC1 drives epithelial-mesenchymal transition in renal carcinoma through Wnt/β-catenin pathway and interaction with SNAIL promoter

Cancer Lett. 2014 May 1;346(2):225-36. doi: 10.1016/j.canlet.2013.12.029. Epub 2013 Dec 30.

Abstract

MUC1 is overexpressed in human carcinomas. The transcription factor SNAIL can activate epithelial-mesenchymal transition (EMT) in cancer cells. In this study, in renal carcinoma, we demonstrate that (i) MUC1 and SNAIL were overexpressed in human sarcomatoid carcinomas, (ii) SNAIL increased indirectly MUC1 expression, (iii) MUC1 overexpression induced EMT, (iv) MUC1 C-terminal domain (MUC1-C) and β-catenin increased SNAIL transcriptional activity by interaction with its promoter and (v) blocking MUC1-C nuclear localization decreased Wnt/β-catenin signaling pathway activation and SNAIL expression. Altogether, our findings demonstrate that MUC1 is an actor in EMT and appears as a new therapeutic target.

Keywords: Beta catenin; Epithelial mesenchymal transition; GO-203; MUC1; SNAIL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology*
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Epithelial-Mesenchymal Transition
  • HEK293 Cells
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology*
  • Mucin-1 / biosynthesis*
  • Mucin-1 / genetics
  • Promoter Regions, Genetic
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Snail Family Transcription Factors
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Transcriptional Activation
  • Up-Regulation
  • Wnt Proteins / metabolism*
  • Wnt Signaling Pathway
  • beta Catenin / metabolism*

Substances

  • CTNNB1 protein, human
  • MUC1 protein, human
  • Mucin-1
  • RNA, Messenger
  • Snail Family Transcription Factors
  • Transcription Factors
  • Wnt Proteins
  • beta Catenin