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

Kun-yong Kim1, Ahmi Baek, Ji-Eun Hwang

  • 1Department of Life Science, Research Center for Women's Diseases, Sookmyung Women's University, Seoul, Korea.

Cancer Research
|April 16, 2009
PubMed

Insights

Adiponectin, a protein linked to lower cancer risk, inhibits breast cancer cell invasion. It activates protein phosphatase 2A (PP2A), a tumor suppressor, by influencing its B56gamma subunit.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Low serum adiponectin levels are associated with increased risk for multiple cancers.
  • Adiponectin is known to inhibit breast cancer cell proliferation and metastasis, but the specific molecular pathways are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which adiponectin suppresses breast cancer cell invasiveness.
  • To investigate the role of AMP-activated protein kinase (AMPK) and protein phosphatase 2A (PP2A) in adiponectin's anti-cancer effects.

Main Methods:

  • Utilized MDA-MB-231 breast cancer cells to study adiponectin signaling.
  • Investigated the phosphorylation of PP2A's B56gamma subunit by AMPK.
  • Assessed PP2A activity and AKT phosphorylation.
  • Measured adiponectin and PP2A activity levels in breast cancer patient samples.

Main Results:

  • Adiponectin activation of AMPK led to decreased invasiveness in MDA-MB-231 cells.
  • AMPK directly phosphorylated B56gamma at Ser(298) and Ser(336), enhancing PP2A activity.
  • This process involved the dephosphorylation of PP2Ac at Tyr(307).
  • Breast cancer patients exhibited lower blood adiponectin and tissue PP2A activity.
  • Direct adiponectin administration increased tumor tissue PP2A activity.

Conclusions:

  • Adiponectin negatively regulates breast cancer cell invasiveness via the AMPK/PP2A pathway.
  • Adiponectin activates the tumor suppressor PP2A, reducing cancer cell metastasis.
  • These findings highlight adiponectin as a potential therapeutic target in breast cancer treatment.

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