The phosphatase PPM1A inhibits triple negative breast cancer growth by blocking cell cycle progression

NPJ Breast Cancer
Abhijit MazumdarPowel H Brown

Abstract

Estrogen receptor (ER)-negative, progesterone receptor (PR)-negative and HER2-negative, or "triple negative," breast cancer (TNBC) is a poor prognosis clinical subtype that occurs more frequently in younger women and is commonly treated with toxic chemotherapy. Effective targeted therapy for TNBC is urgently needed. Our previous studies have identified several kinases critical for TNBC growth. Since phosphatases regulate the function of kinase signaling pathways, we sought to identify critical growth-regulatory phosphatases that are expressed differentially in ER-negative, as compared to ER-positive, breast cancers. In this study, we examined the role of one of these differentially expressed phosphatases, the protein phosphatase Mg + 2/Mn + 2 dependent 1A (PPM1A) which is underexpressed in ER-negative breast cancer as compared to ER-positive breast cancers, in regulating TNBC growth. We found that PPM1A is deleted in ~40% of ER-negative breast cancers, and that induced expression of PPM1A suppresses in vitro and in vivo growth of TNBC cells. This study demonstrates that induction of PPM1A expression blocks the cell cycle and reduces CDK and Rb phosphorylation. These results suggest PPM1A is a crucial regulator of cell cycle pro...Continue Reading

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Datasets Mentioned

BETA
MDA-MB-231

Methods Mentioned

BETA
xenografts
xenograft
flow cytometry
immunoprecipitation
PCR

Software Mentioned

MetaXpress
cBioPortal
Oncomine

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