Adiponectin-activated AMPK stimulates dephosphorylation of AKT through protein phosphatase 2A activation

Kun Yong Kim, Ahmi Baek, Ji Eun Hwang, Yeon A. Choi, Joon Jeong, Myeong Sok Lee, Dea Ho Cho, Jong Seok Lim, Keun Il Kim, Young Yang

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87 Citations (Scopus)

Abstract

Low serum levels of adiponectin are a high risk factor for various types of cancer. Although adiponectin inhibits proliferation and metastasis of breast cancer cells, the underlying molecular mechanisms remain obscure. In this study, we show that adiponectin-activated AMPK reduces the invasiveness of MDA-MB-231 cells by stimulating dephosphorylation of AKT by increasing protein phosphatase 2A (PP2A) activity. Among the various regulatory B56 subunits, B56& gammal was directly phosphorylated by AMPK at Ser 298 and Ser 336, leading to an increase of PP2A activity through dephosphorylation of PP2Ac at Tyr 307. We also show that both the blood levels of adiponectin and the tissue levels of PP2A activity were decreased in breast cancer patients and that the direct administration of adiponectin into tumor tissues stimulates PP2A activity. Taken together, these findings show that adiponectin, derived from adipocytes, negatively regulates the invasiveness of breast cancer cells by activating the tumor suppressor PP2A.

Original languageEnglish
Pages (from-to)4018-4026
Number of pages9
JournalCancer Research
Volume69
Issue number9
DOIs
Publication statusPublished - 2009 May 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Kim, K. Y., Baek, A., Hwang, J. E., Choi, Y. A., Jeong, J., Lee, M. S., Cho, D. H., Lim, J. S., Kim, K. I., & Yang, Y. (2009). Adiponectin-activated AMPK stimulates dephosphorylation of AKT through protein phosphatase 2A activation. Cancer Research, 69(9), 4018-4026. https://doi.org/10.1158/0008-5472.CAN-08-2641