NASP Promotes Triple-negative Breast Cancer Progression and Metastasis by Stabilizing YAP in a USP15-Dependent Way

被引：0

作者：

Zheng, Wenfang ^{[1
]}

Luo, Qifeng ^{[1
]}

Wang, Xuehui ^{[1
]}

Zhou, Xiqian ^{[1
]}

Ye, Danrong ^{[1
]}

Hua, Kaiyao ^{[1
]}

Fang, Lin ^{[1
]}

机构：

[1] Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Breast & Thyroid Surg, 301 Yanchangzhong Rd, Shanghai 200072, Peoples R China

来源：

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2025年 / 21卷 / 09期

基金：

中国国家自然科学基金;

关键词：

triple-negative breast cancer; NASP; USP15; YAP; metastasis; TRANSLATION; EXPRESSION; YAP/TAZ; PROTEIN; PHOSPHORYLATION; PATHWAY; USP15;

D O I：

10.7150/ijbs.99438

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Triple-negative breast cancer (TNBC) was a subtype of breast cancer with high rate of metastasis and poor prognosis. Thus, it is urgent to explore the underlying mechanism of TNBC metastasis and seek for potential therapeutic targets to improve the prognosis of TNBC patients. Here we reported that nuclear autoantigenic sperm protein (NASP) was highly expressed in TNBC and related to poor prognosis of TNBC patients. NASP acted as an oncogene that promoted the progression and metastasis of TNBC. Mechanistically, high expression of NASP in TNBC was induced by SRSF1-mediated stabilization of NASP mRNA. NASP interacted with USP15 and facilitated its activity, which resulted in the deubiquitylation and stabilization of YAP by erasing K48-linked polyubiquitination. Moreover, in vivo studies validated the role of NASP in stimulating TNBC growth and metastasis. Altogether, NASP promoted TNBC progression and metastasis by stabilizing YAP in a USP15-dependent way. It might provide new insights and potential therapeutic targets for preventing TNBC metastasis and improving the prognosis of TNBC patients.

引用

页码：4172 / 4186

页数：15

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