机构：[1]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China[2]Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA[3]The University of Texas Graduate School of Biomedical Sciences at Houston, Texas, USA[4]Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan[5]Department of Pathology, Taipei Medical University Hospital, Taipei, Taiwan[6]Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA[7]Department of Medicine, Baylor College of Medicine, Houston, Texas, USA[8]Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
Angiomotin (AMOT) is a family of proteins found to be a component of the apical junctional complex of vertebrate epithelial cells and is recently found to play important roles in neurofibromatosis type 2 (NF-2). Whether AMOT plays a role in prostate cancer (PCa) is unknown. AMOT is expressed as two isoforms, AMOTp80 and AMOTp130, which has a 409 aa N-terminal domain that is absent in AMOTp80. Both AMOTp80 and AMOTp130 are expressed in LNCaP and C4-2B4, but at a low to undetectable level in PC3, DU145, and BPH1 cells. Further study showed that AMOTp130 and AMOTp80 have distinct functions in PCa cells. We found that AMOTp80, but not AMOT p130, functioned as a tumor promoter by enhancing PCa cell proliferation. Mechanistic studies showed that AMOTp80 signaled through the Hippo pathway by promoting nuclear translocation of YAP, resulting in an increased expression of YAP target protein BMP4. Moreover, inhibition of BMP receptor activity by LDN-193189 abrogates AMOTp80-mediated cell proliferation. Together, this study reveals a novel mechanism whereby the AMOTp80-Merlin-MST1-LATS-YAP-BMP4 pathway leads to AMOTp80-induced tumor cell proliferation.
基金：
National Natural Science Foundation of China (NSFC)National Natural Science Foundation of China [81672547, 81402110]; Science and Technology Support Program of Sichuan Province [2015SZ0230]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01CA174798]; prostate cancer SPORE [P50 CA140388]; Cancer Prevention and Research Institute of Texas [CPRIT RP110327, RP150179]; Prostate Cancer Foundation; cancer center core grant [CA16672]
语种：
外文
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|2 区医学
小类|2 区肿瘤学3 区细胞生物学
最新[2023]版：
无
第一作者：
第一作者机构：[1]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
通讯作者：
通讯机构：[1]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China[2]Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA[3]The University of Texas Graduate School of Biomedical Sciences at Houston, Texas, USA[8]Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
推荐引用方式(GB/T 7714)：
Zeng Hao,Ortiz Angelica,Shen Peng-Fei,et al.Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway.[J].Oncotarget.2017,8(6):10145-10160.doi:10.18632/oncotarget.14358.
APA：
Zeng Hao,Ortiz Angelica,Shen Peng-Fei,Cheng Chien-Jui,Lee Yu-Chen...&Lin Sue-Hwa.(2017).Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway..Oncotarget,8,(6)
MLA：
Zeng Hao,et al."Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway.".Oncotarget 8..6(2017):10145-10160
