Gain Fat-Lose Metastasis: Converting Invasive Breast Cancer Cells into Adipocytes Inhibits Cancer Metastasis

Cancer Cell. 2019 Jan 14;35(1):17-32.e6. doi: 10.1016/j.ccell.2018.12.002.


Cancer cell plasticity facilitates the development of therapy resistance and malignant progression. De-differentiation processes, such as an epithelial-mesenchymal transition (EMT), are known to enhance cellular plasticity. Here, we demonstrate that cancer cell plasticity can be exploited therapeutically by forcing the trans-differentiation of EMT-derived breast cancer cells into post-mitotic and functional adipocytes. Delineation of the molecular pathways underlying such trans-differentiation has motivated a combination therapy with MEK inhibitors and the anti-diabetic drug Rosiglitazone in various mouse models of murine and human breast cancer in vivo. This combination therapy provokes the conversion of invasive and disseminating cancer cells into post-mitotic adipocytes leading to the repression of primary tumor invasion and metastasis formation.

Keywords: EMT; TGFβ-signaling; adipocyte; adipogenesis; breast cancer; cell plasticity; differentiation therapy; invasion; metastasis; trans-differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology*
  • Adipogenesis
  • Animals
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Transdifferentiation / drug effects*
  • Epithelial-Mesenchymal Transition / drug effects
  • Female
  • Flavonoids / administration & dosage*
  • Flavonoids / pharmacology
  • Humans
  • Mice
  • Neoplasm Metastasis / drug therapy*
  • Neoplasm Transplantation
  • Proto-Oncogene Proteins c-met / metabolism
  • Rosiglitazone / administration & dosage*
  • Rosiglitazone / therapeutic use
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta / metabolism


  • Flavonoids
  • Transforming Growth Factor beta
  • Rosiglitazone
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one