机构：[1]School of Medicine, University of Electronic Science and Technology of China, Chengdu, China四川省人民医院[2]Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China四川省人民医院四川省肿瘤医院[3]Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China四川省人民医院[4]Research Unit for Blindness Prevention of Chinese Academy of Medical Science (2019RU026), Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China四川省人民医院[5]Georgia Cancer Center, Augusta University, Augusta, GA, USA[6]Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, USA
Aims: Prostate cancer (PCa) is the most common type of cancer and a major cause of death in men worldwide. Aberrant Androgen receptor (AR) and PI3K-AKT signaling are very frequent in PCa patients and, therefore, considered as therapeutic targets in the clinic. Sin1 is an essential component of mTORC2 complex, which determines full AKT activation and PCa development in PTEN-/- mice. Here we examined the role of Sin1 in human PCa cell lines and respective tumor samples. Main methods: Western blotting and immunohistochemistry (IHC) were performed to analyze the expression of Sin1-mTORC2-AKT related proteins in human PCa cells, as well as prostate tumors and normal tissue counterparts. Cell viability and invasion assays were also pursued in the presence or not of Sin1 in PCa cells. Immunoprecipitation assays were additionally carried out to examine the interaction of Sin1 with AR. Key findings: We have presently demonstrated that high levels of Sin1 expression in human PCa tissues correlate with cancer progression. Sin1-mediated cell proliferation and invasion of PCa cells occurs by regulating mTORC2-AKT signaling, epithelial-mesenchymal transition and matrix metalloproteinases. Moreover, androgens are able to induce Sin1 expression, which is further translocated to the nucleus of PCa cells. Finally, Sin1 interacts with AR to suppress its transcriptional activity. Significance: Taken together, these data indicate that both Sin1-mediated mTORC2-AKT signaling and Sin1-AR interaction regulate PCa development. Hence, Sin1 may be considered a novel biomarker of PCa progression.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31601137, 81601125, 81790642]; Central University Basic Scientific Research Business Expenses Special Funds [ZYGX2017KYQD169, A03019023801206]; National Key Research and Development Program of China [2016YFC0905200]; Chinese Academy of Medical Sciences [2019-I2M-5-032]
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|3 区医学
小类|3 区医学：研究与实验3 区药学
最新[2023]版：
大类|2 区医学
小类|2 区医学：研究与实验2 区药学
JCR分区：
出版当年[2020]版：
Q1PHARMACOLOGY & PHARMACYQ2MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q1MEDICINE, RESEARCH & EXPERIMENTALQ1PHARMACOLOGY & PHARMACY
第一作者机构：[1]School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
共同第一作者：
通讯作者：
通讯机构：[1]School of Medicine, University of Electronic Science and Technology of China, Chengdu, China[3]Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China[*1]School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
推荐引用方式(GB/T 7714)：
Huang Yunchuanxiang,Feng Guanying,Cai Jingshu,et al.Sin1 promotes proliferation and invasion of prostate cancer cells by modulating mTORC2-AKT and AR signaling cascades[J].LIFE SCIENCES.2020,248:doi:10.1016/j.lfs.2020.117449.
APA：
Huang, Yunchuanxiang,Feng, Guanying,Cai, Jingshu,Peng, Qian,Yang, Zhenglin...&Wang, Ziyan.(2020).Sin1 promotes proliferation and invasion of prostate cancer cells by modulating mTORC2-AKT and AR signaling cascades.LIFE SCIENCES,248,
MLA：
Huang, Yunchuanxiang,et al."Sin1 promotes proliferation and invasion of prostate cancer cells by modulating mTORC2-AKT and AR signaling cascades".LIFE SCIENCES 248.(2020)
医学