Nitric oxide and protein phosphatase 2A provide novel therapeutic opportunities in ER-negative breast cancer

作者：Switzer Christopher H; Glynn Sharon A; Ridnour Lisa A; Cheng Robert Y S; Vitek Michael P; Ambs Stefan; Wink David A^*

来源：Trends in Pharmacological Sciences, 2011, 32(11): 644-651.

DOI：10.1016/j.tips.2011.07.001

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.

• 出版日期2011-11