ECM1 regulates tumor metastasis and CSC-like property through stabilization of β-catenin

Oncogene. 2015 Dec 10;34(50):6055-65. doi: 10.1038/onc.2015.54. Epub 2015 Mar 9.

Abstract

Extracellular Matrix Protein 1 (ECM1) is a marker for tumorigenesis and is correlated with invasiveness and poor prognosis in various types of cancer. However, the functional role of ECM1 in cancer metastasis is unclear. Here, we detected high ECM1 level in breast cancer patient sera that was associated with recurrence of tumor. The modulation of ECM1 expression affected not only cell migration and invasion, but also sphere-forming ability and drug resistance in breast cancer cell lines. In addition, ECM1 regulated the gene expression associated with the epithelial to mesenchymal transition (EMT) progression and cancer stem cell (CSC) maintenance. Interestingly, ECM1 increased β-catenin expression at the post-translational level through induction of MUC1, which was physically associated with β-catenin. Indeed, the association between β-catenin and the MUC1 cytoplasmic tail was increased by ECM1. Furthermore, forced expression of β-catenin altered the gene expression that potentiated EMT progression and CSC phenotype maintenance in the cells. These data provide evidence that ECM1 has an important role in cancer metastasis through β-catenin stabilization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Drug Resistance, Neoplasm
  • Epithelial-Mesenchymal Transition
  • Extracellular Matrix Proteins / physiology*
  • Female
  • Humans
  • Mucin-1 / physiology
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplastic Stem Cells
  • Protein Stability
  • beta Catenin / genetics
  • beta Catenin / physiology*

Substances

  • CTNNB1 protein, human
  • ECM1 protein, human
  • Extracellular Matrix Proteins
  • MUC1 protein, human
  • Mucin-1
  • beta Catenin