Nitric oxide and protein phosphatase 2a provide novel therapeutic opportunities in er-negative breast cancer
Switzer, Christopher H. Glynn, Sharon A. Ridnour, Lisa A. Cheng, Robert Y.-S. Vitek, Michael P. Ambs, Stefan Wink, David A.
Switzer, Christopher H.
Glynn, Sharon A.
Ridnour, Lisa A.
Cheng, Robert Y.-S.
Vitek, Michael P.
Ambs, Stefan
Wink, David A.
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Publication Date
2011-11-01
Type
Article
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Switzer, Christopher H. Glynn, Sharon A.; Ridnour, Lisa A.; Cheng, Robert Y.-S.; Vitek, Michael P.; Ambs, Stefan; Wink, David A. (2011). Nitric oxide and protein phosphatase 2a provide novel therapeutic opportunities in er-negative breast cancer. Trends in Pharmacological Sciences 32 (11), 644-651
Abstract
Basal-like breast cancer is an aggressive disease with limited therapeutic options because these tumors frequently express the 'triple-negative' phenotype. We have recently reported that inducible nitric oxide synthase (NOS2) is a strong predictor of survival in patients with estrogen receptor negative [ER(-)] breast cancer, and that NOS2 expression is correlated with a basal-like phenotype. Recent reports also describe the pro-tumor effects of NO in breast and many other types of cancer. NO promotes cancer progression by activating several oncogenic signaling pathways such as extracellular signal-regulated kinases (ERK)-1/2, phosphoinositide 3-kinases (PI3K)/Akt, and c-Myc. Protein phosphatase 2A (PP2A) is a tumor suppressor that negatively regulates the same cancer-related signaling pathways that are activated by NO. PP2A activity is suppressed in tumor cells, but potential pharmacological agents have recently been described to increase PP2A activity in ER(-) breast cancer cells. We examine here the various functions of NO and PP2A in breast cancer and propose a novel mechanism by which activation of PP2A antagonizes NO signaling that promotes ER(-) breast cancer.
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Publisher
Elsevier BV
Publisher DOI
10.1016/j.tips.2011.07.001
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Attribution-NonCommercial-NoDerivs 3.0 Ireland