title: Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway.
abstract: 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.
authors.affiliation: Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.|The University of Texas Graduate School of Biomedical Sciences at Houston, Texas, USA.
authors.forename: Angelica
authors.initials: A
authors.lastname: Ortiz
authors.affiliation: Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Shen
authors.affiliation: Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Pathology, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chien-Jui
authors.initials: CJ
authors.lastname: Cheng
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Guoyu
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Song-Chang
authors.initials: SC
authors.lastname: Lin
authors.affiliation: Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Yu-Lee
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.|The University of Texas Graduate School of Biomedical Sciences at Houston, Texas, USA.|Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Sue-Hwa
authors.initials: SH
authors.lastname: Lin
mesh_terms: D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000091082:Angiomotins; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D052004:Bone Morphogenetic Protein Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D000090683:Hippo Signaling Pathway; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016513:Mice, SCID; D008840:Microfilament Proteins; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014157:Transcription Factors; D014162:Transfection; D000091102:YAP-Signaling Proteins
chemical_list: C423985:AMOT protein, human; D048868:Adaptor Proteins, Signal Transducing; D000091082:Angiomotins; D000970:Antineoplastic Agents; C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D036341:Intercellular Signaling Peptides and Proteins; C554430:LDN 193189; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D011720:Pyrazoles; D011743:Pyrimidines; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D017346:Protein Serine-Threonine Kinases; D052004:Bone Morphogenetic Protein Receptors
keywords: BMP4; Hippo pathway; YAP; angiomotin; proliferation