2. Academic Validation
  3. Interfering MSN-NONO complex-activated CREB signaling serves as a therapeutic strategy for triple-negative breast cancer

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

  • Sci Adv. 2020 Feb 19;6(8):eaaw9960. doi: 10.1126/sciadv.aaw9960.
Yuanyuan Qin 1 2,  Weilong Chen 1 2,  Guojuan Jiang 1,  Lei Zhou 1 2,  Xiaoli Yang 1,  Hongqi Li 3,  Xueyan He 1,  Han-Lin Wang 4 5,  Yu-Bo Zhou 5,  Shenglin Huang 1,  Suling Liu 1
Affiliations

Affiliations

  • 1 Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Key Laboratory of Breast Cancer in Shanghai, Innovation Center for Cell Signaling Network, Cancer Institutes, Fudan University, Shanghai 200032, China.
  • 2 School of Life Sciences, CAS Key Laboratory of Innate Immunity and Chronic Disease, University of Science and Technology of China, Hefei, Anhui 230027, China.
  • 3 Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 4 School of Life Science and Technology, Shanghai Tech University, Shanghai 201203, China.
  • 5 National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
PMID: 32128390 DOI: 10.1126/sciadv.aaw9960
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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