Interfering MSN-NONO complex-activated CREB signaling serves as a therapeutic strategy for triple-negative breast cancer

Science Advances
Yuanyuan QinSuling Liu

Abstract

Triple-negative breast cancer (TNBC) is life-threatening because of limited therapies and lack of effective therapeutic targets. Here, we found that moesin (MSN) was significantly overexpressed in TNBC compared with other subtypes of breast cancer and was positively correlated with poor overall survival. However, little is known about the regulatory mechanisms of MSN in TNBC. We found that MSN significantly stimulated breast cancer cell proliferation and invasion in vitro and tumor growth in vivo, requiring the phosphorylation of MSN and a nucleoprotein NONO-assisted nuclear localization of phosphorylated MSN with protein kinase C (PKC) and then the phosphorylation activation of CREB signaling by PKC. Our study also demonstrated that targeting MSN, NONO, or CREB significantly inhibited breast tumor growth in vivo. These results introduce a new understanding of MSN function in breast cancer and provide favorable evidence that MSN or its downstream molecules might serve as new targets for TNBC treatment.

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Datasets Mentioned

BETA
GSE2034
GSE9893

Methods Mentioned

BETA
RNA-seq
xenograft
immunoprecipitation
pull down
electrophoresis
nuclear translocation
transfection

Software Mentioned

PROGgeneV2
ImageJ
Xena
GraphPad Prism

Related Concepts

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