CDC25B partners with PP2A to induce AMPK activation and tumor suppression in triple negative breast cancer

Junmei Cairns; Reynold C Ly; Nifang Niu; Krishna R Kalari; Erin E Carlson; Liewei Wang

doi:10.1093/narcan/zcaa039

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CDC25B partners with PP2A to induce AMPK activation and tumor suppression in triple negative breast cancer

Journal article

Open access

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CDC25B partners with PP2A to induce AMPK activation and tumor suppression in triple negative breast cancer

Junmei Cairns, Reynold C Ly, Nifang Niu, Krishna R Kalari, Erin E Carlson and Liewei Wang

NAR cancer, Vol.2(4), pp.zcaa039-zcaa039

12/01/2020

DOI: 10.1093/narcan/zcaa039

PMCID: PMC7751685

PMID: 33385163

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Abstract

Cell division cycle 25 (CDC25) dual specificity phosphatases positively regulate the cell cycle by activating cyclin-dependent kinase/cyclin complexes. Here, we demonstrate that in addition to its role in cell cycle regulation, CDC25B functions as a regulator of protein phosphatase 2A (PP2A), a major cellular Ser/Thr phosphatase, through its direct interaction with PP2A catalytic subunit. Importantly, CDC25B alters the regulation of AMP-activated protein kinase signaling (AMPK) by PP2A, increasing AMPK activity by inhibiting PP2A to dephosphorylate AMPK. CDC25B depletion leads to metformin resistance by inhibiting metformin-induced AMPK activation. Furthermore, dual inhibition of CDC25B and PP2A further inhibits growth of 3D organoids isolated from patient derived xenograft model of breast cancer compared to CDC25B inhibition alone. Our study identifies CDC25B as a regulator of PP2A, and uncovers a mechanism of controlling the activity of a key energy metabolism marker, AMPK.

Cancer Gene Regulation, Chromatin, and Epigenetics

Details

Title: Subtitle: CDC25B partners with PP2A to induce AMPK activation and tumor suppression in triple negative breast cancer
Creators: Junmei Cairns - Mayo Clinic
Reynold C Ly - Indiana University – Purdue University Indianapolis
Nifang Niu - Mayo Clinic
Krishna R Kalari - Mayo Clinic in Florida
Erin E Carlson - Mayo Clinic in Florida
Liewei Wang - Mayo Clinic
Resource Type: Journal article
Publication Details: NAR cancer, Vol.2(4), pp.zcaa039-zcaa039
Publisher: Oxford University Press
DOI: 10.1093/narcan/zcaa039
PMID: 33385163
PMCID: PMC7751685
ISSN: 2632-8674
eISSN: 2632-8674
Grant note: GM072474; R01 CA196648 / ;
Language: English
Date published: 12/01/2020
Academic Unit: Stead Family Department of Pediatrics; Medical Genetics and Genomics
Record Identifier: 9984701551302771

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