Tags

Type your tag names separated by a space and hit enter

Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway.
Oncotarget. 2017 Feb 07; 8(6):10145-10160.O

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+Show Affiliations

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.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 Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Department of Pathology, Taipei Medical University Hospital, Taipei, Taiwan.Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA.Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28052036

Citation

Zeng, Hao, et al. "Angiomotin Regulates Prostate Cancer Cell Proliferation By Signaling Through the Hippo-YAP Pathway." Oncotarget, vol. 8, no. 6, 2017, pp. 10145-10160.
Zeng H, Ortiz A, Shen PF, et al. Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway. Oncotarget. 2017;8(6):10145-10160.
Zeng, H., Ortiz, A., Shen, P. F., Cheng, C. J., Lee, Y. C., Yu, G., Lin, S. C., Creighton, C. J., Yu-Lee, L. Y., & Lin, S. H. (2017). Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway. Oncotarget, 8(6), 10145-10160. https://doi.org/10.18632/oncotarget.14358
Zeng H, et al. Angiomotin Regulates Prostate Cancer Cell Proliferation By Signaling Through the Hippo-YAP Pathway. Oncotarget. 2017 Feb 7;8(6):10145-10160. PubMed PMID: 28052036.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway. AU - Zeng,Hao, AU - Ortiz,Angelica, AU - Shen,Peng-Fei, AU - Cheng,Chien-Jui, AU - Lee,Yu-Chen, AU - Yu,Guoyu, AU - Lin,Song-Chang, AU - Creighton,Chad J, AU - Yu-Lee,Li-Yuan, AU - Lin,Sue-Hwa, PY - 2016/10/11/received PY - 2016/12/13/accepted PY - 2017/1/5/pubmed PY - 2018/2/21/medline PY - 2017/1/5/entrez KW - BMP4 KW - Hippo pathway KW - YAP KW - angiomotin KW - proliferation SP - 10145 EP - 10160 JF - Oncotarget JO - Oncotarget VL - 8 IS - 6 N2 - 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. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/28052036/Angiomotin_regulates_prostate_cancer_cell_proliferation_by_signaling_through_the_Hippo_YAP_pathway_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=14358 DB - PRIME DP - Unbound Medicine ER -