Stat5 promotes homotypic adhesion and inhibits invasive characteristics of human breast cancer cells

Oncogene. 2005 Jan 27;24(5):746-60. doi: 10.1038/sj.onc.1208203.

Abstract

Signal transducer and activator of transcription-5 (Stat5) mediates prolactin (PRL)-induced differentiation and growth of breast epithelial cells. We have recently identified active Stat5 as a tumor marker of favorable prognosis in human breast cancer, and determined that Stat5 activation is lost during metastatic progression. Here we provide novel evidence for an invasion-suppressive role of Stat5 in human breast cancer. Activation of Stat5 by PRL in human breast cancer lines was associated with increased surface levels of the invasion-suppressive adhesion molecule E-cadherin in vitro and in xenotransplant tumors in vivo. Inducible E-cadherin was blocked by dominant-negative (Dn) Stat5 or Dn-Jak2, but not by Dn-Stat3. Further experimental data indicated a role of Stat5 as a coordinate regulator of additional invasion-related characteristics of human breast cancer cells, including cell surface association of beta-catenin, homotypic cell clustering, invasion through Matrigel, cell migration, and matrix metalloproteinase activity. A role of Stat5 as a suppressor of breast cancer invasion and metastatic progression provides a biological mechanism to explain the favorable prognosis associated with active Stat5 in human breast cancer.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Breast Neoplasms / pathology
  • Cadherins / metabolism
  • Cell Adhesion / physiology*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cytoskeletal Proteins / physiology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Female
  • Humans
  • Mice
  • Milk Proteins / genetics
  • Neoplasm Invasiveness / prevention & control*
  • Neoplasm Metastasis
  • Prognosis
  • Prolactin / pharmacology*
  • Recombinant Proteins / metabolism
  • STAT5 Transcription Factor
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Transfection
  • Tumor Suppressor Proteins
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Cadherins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Milk Proteins
  • Recombinant Proteins
  • STAT5 Transcription Factor
  • STAT5A protein, human
  • Trans-Activators
  • Tumor Suppressor Proteins
  • beta Catenin
  • Prolactin