Estrogen promotes prostate cancer cell migration via paracrine release of ENO1 from stromal cells

Mol Endocrinol. 2012 Sep;26(9):1521-30. doi: 10.1210/me.2012-1006. Epub 2012 Jun 25.


As a key glycolytic enzyme, enolase 1 (ENO1) is critical for cellular energy metabolism. Recent studies have revealed its important role in growth and metastasis of lung, head and neck, and breast cancer. However, the regulatory mechanisms of ENO1 expression and secretion remain unclear. We observed that conditioned medium from estradiol-stimulated prostate stromal cells significantly promoted the migration of prostate cancer (PCa) cells. Two-dimensional protein electrophoresis, mass spectrometry, and immunodepletion assays identified one of the major active factors in the conditioned medium as α-type enolase (α-enolase, or ENO1). Moreover, in prostate stromal cells, estradiol not only enhanced the stability of ENO1 at the protein level in an estrogen receptor-α-dependent manner but also promoted its secretion to the extracellular matrix. Furthermore, recombinant ENO1 bound to the surface of PCa cells and promoted cell migration via their plasminogen receptor activity in a paracrine manner. Immunohistochemistry suggested that stromal ENO1 levels increased in PCa compared with those in normal tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Culture Media, Conditioned / pharmacology
  • DNA-Binding Proteins / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Estrogens / pharmacology*
  • Humans
  • Male
  • Phosphopyruvate Hydratase / metabolism*
  • Plasminogen / metabolism
  • Prostatic Neoplasms / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Stromal Cells / metabolism*
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins / metabolism*


  • Biomarkers, Tumor
  • Culture Media, Conditioned
  • DNA-Binding Proteins
  • Estrogens
  • Tumor Suppressor Proteins
  • Plasminogen
  • ENO1 protein, human
  • Phosphopyruvate Hydratase