Adiponectin increases motility of human prostate cancer cells via adipoR, p38, AMPK, and NF-kappaB pathways.
BACKGROUND
Prostate cancer is the most commonly diagnosed malignancy in men. Prostate cancer shows a predilection for metastasis to the bone. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes and involved in energy homeostasis. The aim of this study was to investigate whether adiponectin is associated with migration of prostate cancer cells.


METHODS
Cancer cells migration activity was examined using the Transwell assay. The p38 and AMPK phosphorylation was examined by using Western blot method. The cell surface expression of integrins was examined by using flow cytometry. The qPCR was used to examine the mRNA expression of integrin. A transient transfection protocol was used to examine NF-kappaB activity.


RESULTS
We found that adiponectin increased the migration and the expression of alpha5beta1 integrin of human prostate cancer cells. Adiponectin-mediated migration and integrins expression was attenuated by p38 inhibitor (SB203580), p38 mutant, AMPK siRNA, AMPK inhibitor (araA and compound C). Activations of p38, AMPK and NF-kappaB pathways after adiponectin treatment was demonstrated, and adiponectin-induced expression of integrins and migration activity was inhibited by the specific inhibitor and mutant of p38, AMPK, and NF-kappaB cascades.


CONCLUSIONS
This study showed for the first time that the adiponectin mediates migration of human prostate cancer cells. One of the mechanisms underlying adiponectin directed migration was transcriptional up-regulation of alpha5beta1 integrin and activation of AdipoR1 receptor, p38, AMPK, and NF-kappaB pathways.
Tang
Chih-Hsin
CH
Department of Pharmacology, China Medical University, Taichung, Taiwan. chtang@mail.cmu.edu.tw
Lu
Mu-En
ME
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052242:Adiponectin / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D011494:Protein Kinases / Q000378:metabolism*; D054419:Receptors, Adiponectin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D052242:Adiponectin; D039081:Integrin alpha5beta1; D016328:NF-kappa B; D054419:Receptors, Adiponectin; D011494:Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases