Growth and differentiation factor 9 (GDF-9) induces epithelial-mesenchymal transition in prostate cancer cells.
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.
Department of Surgery, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
Sivan M
SM
Bokobza
Lin
L
Ye
Howard
H
Kynaston
Wen G
WG
Jiang
D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D004789:Enzyme Activation; D058750:Epithelial-Mesenchymal Transition; D055785:Gene Knockdown Techniques; D055429:Growth Differentiation Factor 9 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic; D051879:Twist-Related Protein 1 / Q000235:genetics; D015854:Up-Regulation; D020741:rho GTP-Binding Proteins / Q000096:biosynthesis; D054460:rho-Associated Kinases / Q000235:genetics; D000075024:rhoC GTP-Binding Protein
D015820:Cadherins; D055429:Growth Differentiation Factor 9; D009687:Nuclear Proteins; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D017346:Protein Serine-Threonine Kinases; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein