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Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354648/ https://www.ncbi.nlm.nih.gov/pubmed/28052036 http://dx.doi.org/10.18632/oncotarget.14358 |
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author | Zeng, Hao Ortiz, Angelica Shen, Peng-Fei Cheng, Chien-Jui Lee, Yu-Chen Yu, Guoyu Lin, Song-Chang Creighton, Chad J. Yu-Lee, Li-Yuan Lin, Sue-Hwa |
author_facet | Zeng, Hao Ortiz, Angelica Shen, Peng-Fei Cheng, Chien-Jui Lee, Yu-Chen Yu, Guoyu Lin, Song-Chang Creighton, Chad J. Yu-Lee, Li-Yuan Lin, Sue-Hwa |
author_sort | Zeng, Hao |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5354648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53546482017-04-14 Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway Zeng, Hao Ortiz, Angelica Shen, Peng-Fei Cheng, Chien-Jui Lee, Yu-Chen Yu, Guoyu Lin, Song-Chang Creighton, Chad J. Yu-Lee, Li-Yuan Lin, Sue-Hwa Oncotarget Research Paper 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. Impact Journals LLC 2016-12-29 /pmc/articles/PMC5354648/ /pubmed/28052036 http://dx.doi.org/10.18632/oncotarget.14358 Text en Copyright: © 2017 Zeng et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Zeng, Hao Ortiz, Angelica Shen, Peng-Fei Cheng, Chien-Jui Lee, Yu-Chen Yu, Guoyu Lin, Song-Chang Creighton, Chad J. Yu-Lee, Li-Yuan Lin, Sue-Hwa Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway |
title | Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway |
title_full | Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway |
title_fullStr | Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway |
title_full_unstemmed | Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway |
title_short | Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway |
title_sort | angiomotin regulates prostate cancer cell proliferation by signaling through the hippo-yap pathway |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354648/ https://www.ncbi.nlm.nih.gov/pubmed/28052036 http://dx.doi.org/10.18632/oncotarget.14358 |
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