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

IF 8.2 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biological Sciences Pub Date : 2025-06-20 eCollection Date: 2025-01-01 DOI:10.7150/ijbs.99438

Wenfang Zheng, Qifeng Luo, Xuehui Wang, Xiqian Zhou, Danrong Ye, Kaiyao Hua, Lin Fang

{"title":"NASP Promotes Triple-negative Breast Cancer Progression and Metastasis by Stabilizing YAP in a USP15-Dependent Way.","authors":"Wenfang Zheng, Qifeng Luo, Xuehui Wang, Xiqian Zhou, Danrong Ye, Kaiyao Hua, Lin Fang","doi":"10.7150/ijbs.99438","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 9","pages":"4172-4186"},"PeriodicalIF":8.2000,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223775/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Biological Sciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.7150/ijbs.99438","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

NASP通过稳定YAP以usp15依赖的方式促进三阴性乳腺癌进展和转移。

三阴性乳腺癌（TNBC）是一种转移率高、预后差的乳腺癌亚型。因此，迫切需要探索TNBC转移的潜在机制，寻找潜在的治疗靶点，以改善TNBC患者的预后。本研究报告核自体抗原精子蛋白（NASP）在TNBC中高表达，与TNBC患者预后不良有关。NASP作为癌基因促进TNBC的进展和转移。在机制上，srsf1介导的NASP mRNA稳定诱导了TNBC中NASP的高表达。NASP与USP15相互作用，促进其活性，通过消除k48连接的多泛素化，导致YAP去泛素化和稳定。此外，体内研究证实了NASP在刺激TNBC生长和转移中的作用。总的来说，NASP通过稳定YAP以usp15依赖的方式促进TNBC的进展和转移。这可能为预防TNBC转移和改善TNBC患者预后提供新的见解和潜在的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

International Journal of Biological Sciences 生物-生化与分子生物学

CiteScore

16.90

自引率

1.10%

发文量

413

审稿时长

1 months

期刊介绍： The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.