Growth and differentiation factor 9 (GDF-9) induces epithelial-mesenchymal transition in prostate cancer cells

Mol Cell Biochem. 2011 Mar;349(1-2):33-40. doi: 10.1007/s11010-010-0657-5. Epub 2010 Nov 30.

Abstract

The role of bone morphogenetic proteins in the progression and metastasis of prostate cancer is a topic that has undergone extensive research. This study investigates the role of BMP member growth and differentiation factor 9 (GDF-9) in the progression of this disease. GDF-9 was over-expressed and knocked-down in PC-3 cells, respectively. Furthermore, along with the use of a generated recombinant GDF-9 protein, these cells were then analyzed for any changes in their invasiveness and expression of epithelial-mesenchymal transition (EMT) associated genes. GDF-9 was shown to promote the invasiveness of PC-3 cells together with an induction in the expression of genes including SNAI1, RhoC, ROCK-1, and N-cadherin, while reducing levels of E-cadherin. These expression changes are characteristic of the onset of EMT, and resulted in the cells having a more mesenchymal-like morphology. Treating these cells with activin-like kinase-5 (ALK-5) inhibitor, demonstrated that GDF-9 induced up-regulation of these molecules was ALK-5 dependant. This study shows that in PC-3 cells, GDF-9 signaling via ALK-5, can promote cell invasiveness via a complex network of signaling molecules that work together to trigger the process of EMT, and thereby aid in the aggressiveness and progression of prostate cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / biosynthesis
  • Cadherins / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Enzyme Activation
  • Epithelial-Mesenchymal Transition*
  • Gene Knockdown Techniques
  • Growth Differentiation Factor 9 / genetics
  • Growth Differentiation Factor 9 / metabolism*
  • Humans
  • Male
  • Neoplasm Invasiveness
  • Nuclear Proteins / genetics
  • Phosphorylation
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Snail Family Transcription Factors
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription, Genetic
  • Twist-Related Protein 1 / genetics
  • Up-Regulation
  • rho GTP-Binding Proteins / biosynthesis
  • rho-Associated Kinases / genetics
  • rhoC GTP-Binding Protein

Substances

  • Cadherins
  • Growth Differentiation Factor 9
  • Nuclear Proteins
  • Receptors, Transforming Growth Factor beta
  • Recombinant Proteins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • TWIST1 protein, human
  • Transcription Factors
  • Twist-Related Protein 1
  • Protein-Serine-Threonine Kinases
  • ROCK1 protein, human
  • rho-Associated Kinases
  • Receptor, Transforming Growth Factor-beta Type I
  • TGFBR1 protein, human
  • RHOC protein, human
  • rho GTP-Binding Proteins
  • rhoC GTP-Binding Protein