Trop-2 plasticity is controlled by epithelial-to-mesenchymal transition

Carcinogenesis. 2018 Dec 13;39(11):1411-1418. doi: 10.1093/carcin/bgy095.


The cell surface glycoprotein Trop-2 is commonly overexpressed in carcinomas and represents an exceptional antigen for targeted therapy. Here, we provide evidence that surface Trop-2 expression is functionally connected with an epithelial phenotype in breast and prostate cell lines and in patient tumor samples. We further show that Trop-2 expression is suppressed epigenetically or through the action of epithelial-to-mesenchymal transition transcription factors and that deregulation of Trop-2 expression is linked with cancer progression and poor patient prognosis. Moreover, our data suggest that the cancer plasticity-driven intratumoral heterogeneity in Trop-2 expression may significantly contribute to response and resistance to therapies targeting Trop-2-expressing cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Cadherins / biosynthesis
  • Carcinoma / pathology*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • DNA Methylation / genetics
  • Disease Progression
  • Epithelial Cells / metabolism*
  • Epithelial-Mesenchymal Transition / physiology
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology*
  • Xenograft Model Antitumor Assays


  • Antigens, CD
  • Antigens, Neoplasm
  • CDH1 protein, human
  • Cadherins
  • Cell Adhesion Molecules
  • TACSTD2 protein, human