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

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to limited treatment options and a lack of effective targets.
• Moesin (MSN) is frequently overexpressed in TNBC and is associated with poorer patient survival, indicating its potential role in TNBC pathogenesis.
• The precise regulatory mechanisms governing MSN's function in TNBC remain largely unexplored.

Purpose of the Study:

• To elucidate the role and regulatory mechanisms of moesin (MSN) in triple-negative breast cancer (TNBC).
• To investigate the potential of targeting MSN and its associated signaling pathway as a therapeutic strategy for TNBC.

Main Methods:

• Investigated moesin (MSN) expression levels in TNBC compared to other breast cancer subtypes.
• Assessed the impact of MSN on cancer cell proliferation, invasion, and tumor growth in vitro and in vivo.
• Utilized techniques to study the phosphorylation of MSN, its nuclear localization mediated by NONO, and the activation of CREB signaling via protein kinase C (PKC).

Main Results:

• Moesin (MSN) was found to be significantly overexpressed in TNBC and correlated with poor overall survival.
• Phosphorylated MSN, facilitated by NONO for nuclear localization and subsequent PKC-mediated activation of CREB signaling, significantly promoted breast cancer cell proliferation, invasion, and tumor growth.
• Targeting MSN, NONO, or CREB effectively inhibited tumor growth in vivo.

Conclusions:

• Moesin (MSN) plays a critical role in promoting TNBC progression through a pathway involving NONO and CREB signaling.
• This study provides novel insights into the function of MSN in breast cancer.
• MSN and its downstream effectors (NONO, CREB) represent promising therapeutic targets for the treatment of triple-negative breast cancer.