423회 Adipocytes regulates metastasis of breast cancer cells through ad…

423회 (2009. 3. 12.)

연사: 양 영, 숙명여자대학교

제목:  Adipocytes regulates metastasis of breast cancer cells through dipokines  

Abstract 

Low serum levels of adiponectin are a high risk factorfor various types of cancer, including prostate, colorectal, endometrial, and breast cancer. Although adiponectin inhibits proliferation and metastasis of breast cancer cells, underlying molecular mechanism remains obscured. In this study, we showed that adiponectin suppressed expression and activity of urokinase-type plasminogen activator and matrix metalloprotease 2 and 9,while the level of the metastasis suppressor gene, tissue inhibitor of matrix metalloprotease 1, was significantly increased in the human breast cancer cell line MDA-MB-231. In addition, we demonstrated that adiponectin-activated AMPK was involved in dephosphorylation of AKT. Since AMPK is a kinase, it was examined whether AMPK is able to activate protein phosphatase 2A (PP2A). PP2A activity was increasedby adiponectin treatment and also by recombinant AMPK, resulting in the dephosphorylation of AKT on Ser473. Among various regulatory B56 subunit, B56γ, B56β, and B56δwere directly phosphorylated by AMPK, resulting in increase of PP2A activity. Taken together, weshow that adiponectin- activated AMPK increases the B56γ-specific PP2A holoenzyme activity, resulting in inactivation of AKT by dephosphorylation.