USP11 Enhances TGFβ-Induced Epithelial-Mesenchymal Plasticity and Human Breast Cancer Metastasis

Mol Cancer Res. 2018 Jul;16(7):1172-1184. doi: 10.1158/1541-7786.MCR-17-0723. Epub 2018 May 3.


Epithelial-mesenchymal transition (EMT) is a conserved cellular plasticity program that is reactivated in carcinoma cells and drives metastasis. Although EMT is well studied its regulatory mechanisms remain unclear. Therefore, to identify novel regulators of EMT, a data mining approach was taken using published microarray data and a group of deubiquitinases (DUB) were found to be upregulated in cells that have undergone EMT. Here, it is demonstrated that one DUB, ubiquitin-specific peptidase 11 (USP11), enhances TGFβ-induced EMT and self-renewal in immortalized human mammary epithelial cells. Furthermore, modulating USP11 expression in human breast cancer cells altered the migratory capacity in vitro and metastasis in vivo Moreover, elevated USP11 expression in human breast cancer patient clinical specimens correlated with decreased survival. Mechanistically, modulating USP11 expression altered the stability of TGFβ receptor type II (TGFBR2) and TGFβ downstream signaling in human breast cancer cells. Together, these data suggest that deubiquitination of TGFBR2 by USP11 effectively spares TGFBR2 from proteasomal degradation to promote EMT and metastasis.Implications: USP11 regulates TGFβ-induced epithelial-mesenchymal plasticity and human breast cancer metastasis and may be a potential therapeutic target for breast cancer. Mol Cancer Res; 16(7); 1172-84. ©2018 AACR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Plasticity / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Metastasis
  • Receptor, Transforming Growth Factor-beta Type II / genetics*
  • Signal Transduction / genetics
  • Thiolester Hydrolases / genetics*
  • Transforming Growth Factor beta / genetics*


  • Transforming Growth Factor beta
  • USP11 protein, human
  • Receptor, Transforming Growth Factor-beta Type II
  • TGFBR2 protein, human
  • Thiolester Hydrolases