Stabilization of Notch1 and beta-catenin in response to ER- breast cancer-specific up-regulation of PSAT1 mediates distant metastasis

作者全名："Zhu, Shuxuan; Wang, Xiaoyu; Liu, Lei; Ren, Guosheng"

作者地址："[Zhu, Shuxuan; Wang, Xiaoyu; Liu, Lei; Ren, Guosheng] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Mol Oncol & Epigenet, Chongqing, Peoples R China; [Zhu, Shuxuan; Wang, Xiaoyu; Ren, Guosheng] Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrine & Breast Surg, Chongqing, Peoples R China"

通信作者："Liu, L; Ren, GS (通讯作者)，1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：TRANSLATIONAL ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000820874600003

JCR分区：Q1

影响因子：5

年份：2022

卷号：20

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：PSAT1; breast cancer; metastasis; Notch1; beta-catenin

摘要："Breast cancer has the highest incidence in women worldwide, with a mortality rate second only to lung cancer. Distant metastasis is the major cause of breast cancer-induced death. While upregulation of phosphoserine aminotransferase 1 (PSAT1) has been reported in several cancer types, its specific roles in breast cancer and potential involvement in distant metastasis remain unclear. In our study, PSAT1 was upregulated in metastatic breast cancer and promoted distant metastasis both in vitro and in vivo. Data obtained from transwell and wound healing, colony, sphere assays and detection of various malignant phenotypic markers showed that PSAT1 mediates distant metastasis by promoting invasion, migration, proliferation, anti-apoptosis, stemness and angiogenesis in breast cancer cells. Mechanistically, PSAT1 activated Notch and beta-catenin signaling pathways, leading to enhanced distant metastasis. The clinical relevance of PSAT1 in breast cancer was additionally investigated, which revealed associations of poorer patient prognosis with high PSAT1 mRNA and protein expression. In summary, PSAT1 is a critical molecular regulator of distant metastasis that may effectively serve as a marker of poor prognosis in breast cancer."

基金机构："Natural Science Foundation of China [31420103915, 81902965]; Chongqing Youth Talent Support Program [CQYC2020057957]; Youth Talent Support Program of the First Affifiliated Hospital of Chongqing Medical University [BJRC2020-01]; Future Medical Youth Innovation Team Project of Chongqing Medical University [W0042]; First Affifiliated Hospital of Chongqing Medical University cultivating fund [PYJJ2019-202, PYJJ2019-203]"

基金资助正文："` This work was supported by the Natural Science Foundation of China (31420103915, 81902965); the Chongqing Youth Talent Support Program (CQYC2020057957); the Youth Talent Support Program of the First Affifiliated Hospital of Chongqing Medical University (BJRC2020-01); Future Medical Youth Innovation Team Project of Chongqing Medical University (W0042);The First Affifiliated Hospital of Chongqing Medical University cultivating fund (PYJJ2019-202, PYJJ2019-203)."