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.
METHOD.
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
themRNAexpression of integrin.Atransient transfection protocol was used to examine NF-
kB
activity.
RESULTS.
We found that adiponectin increased the migration and the expression of a5b1
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-
kB 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-
kB
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
a5b1 integrin and activation of AdipoR1
receptor, p38, AMPK, and NF-
kB pathways. Prostate # 2009 Wiley-Liss, Inc.