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

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.

• Authors: Sivan M Bokobza, Lin Ye, Howard Kynaston, Wen G Jiang
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 349 Issue 1-2 Pg. 33-40 (Mar 2011) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 21116689 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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