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Membrane microdomain-associated uroplakin IIIa contributes to Src-dependent mechanisms of anti-apoptotic proliferation in human bladder carcinoma cells
Our previous study demonstrated that tyrosine phosphorylation of p145(met)/β-subunit of hepatocyte growth factor receptor by epidermal growth factor receptor and Src contributes to the anti-apoptotic growth of human bladder carcinoma cell 5637 under serum-starved conditions. Here, we show that some...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507173/ https://www.ncbi.nlm.nih.gov/pubmed/23213380 http://dx.doi.org/10.1242/bio.20121115 |
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author | Kihira, Shigeru Yoshida, Junpei Kawada, Yukari Hitomi, Yuriko Asada, Tomohisa Hisatomi, Rie Ohta, Akina Iwasaki, Tetsushi Mahbub Hasan, A. K. M. Fukami, Yasuo Sato, Ken-ichi |
author_facet | Kihira, Shigeru Yoshida, Junpei Kawada, Yukari Hitomi, Yuriko Asada, Tomohisa Hisatomi, Rie Ohta, Akina Iwasaki, Tetsushi Mahbub Hasan, A. K. M. Fukami, Yasuo Sato, Ken-ichi |
author_sort | Kihira, Shigeru |
collection | PubMed |
description | Our previous study demonstrated that tyrosine phosphorylation of p145(met)/β-subunit of hepatocyte growth factor receptor by epidermal growth factor receptor and Src contributes to the anti-apoptotic growth of human bladder carcinoma cell 5637 under serum-starved conditions. Here, we show that some other cell lines of human bladder carcinoma, but not other types of human cancer cells, also exhibit Src-dependent, anti-apoptotic proliferation under serum-starved conditions, and that low-density, detergent-insoluble membrane microdomains (MD) serve as a structural platform for signaling events involving p145(met), EGFR, and Src. As an MD-associated molecule that may contribute to bladder carcinoma-specific cellular function, we identified uroplakin IIIa (UPIIIa), an urothelium-specific protein. Results obtained so far revealed: 1) UPIIIa undergoes partial proteolysis in serum-starved cells; 2) a specific antibody to the extracellular domain of UPIIIa inhibits the proteolysis of UPIIIa and the activation of Src, and promotes apoptosis in serum-starved cells; and 3) knockdown of UPIIIa by short interfering RNA also promotes apoptosis in serum-starved cells. GM6001, a potent inhibitor of matrix metalloproteinase (MMP), inhibits the proteolysis of UPIIIa and promotes apoptosis in serum-starved cells. Furthermore, serum starvation promotes expression and secretion of the heparin-binding EGF-like growth factor in a manner that depends on the functions of MMP, Src, and UPIIIa. These results highlight a hitherto unknown signaling network involving a subset of MD-associated molecules in the anti-apoptotic mechanisms of human bladder carcinoma cells. |
format | Online Article Text |
id | pubmed-3507173 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Company of Biologists |
record_format | MEDLINE/PubMed |
spelling | pubmed-35071732012-12-04 Membrane microdomain-associated uroplakin IIIa contributes to Src-dependent mechanisms of anti-apoptotic proliferation in human bladder carcinoma cells Kihira, Shigeru Yoshida, Junpei Kawada, Yukari Hitomi, Yuriko Asada, Tomohisa Hisatomi, Rie Ohta, Akina Iwasaki, Tetsushi Mahbub Hasan, A. K. M. Fukami, Yasuo Sato, Ken-ichi Biol Open Research Article Our previous study demonstrated that tyrosine phosphorylation of p145(met)/β-subunit of hepatocyte growth factor receptor by epidermal growth factor receptor and Src contributes to the anti-apoptotic growth of human bladder carcinoma cell 5637 under serum-starved conditions. Here, we show that some other cell lines of human bladder carcinoma, but not other types of human cancer cells, also exhibit Src-dependent, anti-apoptotic proliferation under serum-starved conditions, and that low-density, detergent-insoluble membrane microdomains (MD) serve as a structural platform for signaling events involving p145(met), EGFR, and Src. As an MD-associated molecule that may contribute to bladder carcinoma-specific cellular function, we identified uroplakin IIIa (UPIIIa), an urothelium-specific protein. Results obtained so far revealed: 1) UPIIIa undergoes partial proteolysis in serum-starved cells; 2) a specific antibody to the extracellular domain of UPIIIa inhibits the proteolysis of UPIIIa and the activation of Src, and promotes apoptosis in serum-starved cells; and 3) knockdown of UPIIIa by short interfering RNA also promotes apoptosis in serum-starved cells. GM6001, a potent inhibitor of matrix metalloproteinase (MMP), inhibits the proteolysis of UPIIIa and promotes apoptosis in serum-starved cells. Furthermore, serum starvation promotes expression and secretion of the heparin-binding EGF-like growth factor in a manner that depends on the functions of MMP, Src, and UPIIIa. These results highlight a hitherto unknown signaling network involving a subset of MD-associated molecules in the anti-apoptotic mechanisms of human bladder carcinoma cells. The Company of Biologists 2012-08-17 /pmc/articles/PMC3507173/ /pubmed/23213380 http://dx.doi.org/10.1242/bio.20121115 Text en © 2012. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by-nc-sa/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Article Kihira, Shigeru Yoshida, Junpei Kawada, Yukari Hitomi, Yuriko Asada, Tomohisa Hisatomi, Rie Ohta, Akina Iwasaki, Tetsushi Mahbub Hasan, A. K. M. Fukami, Yasuo Sato, Ken-ichi Membrane microdomain-associated uroplakin IIIa contributes to Src-dependent mechanisms of anti-apoptotic proliferation in human bladder carcinoma cells |
title | Membrane microdomain-associated uroplakin IIIa contributes to Src-dependent mechanisms of anti-apoptotic proliferation in human bladder carcinoma cells |
title_full | Membrane microdomain-associated uroplakin IIIa contributes to Src-dependent mechanisms of anti-apoptotic proliferation in human bladder carcinoma cells |
title_fullStr | Membrane microdomain-associated uroplakin IIIa contributes to Src-dependent mechanisms of anti-apoptotic proliferation in human bladder carcinoma cells |
title_full_unstemmed | Membrane microdomain-associated uroplakin IIIa contributes to Src-dependent mechanisms of anti-apoptotic proliferation in human bladder carcinoma cells |
title_short | Membrane microdomain-associated uroplakin IIIa contributes to Src-dependent mechanisms of anti-apoptotic proliferation in human bladder carcinoma cells |
title_sort | membrane microdomain-associated uroplakin iiia contributes to src-dependent mechanisms of anti-apoptotic proliferation in human bladder carcinoma cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507173/ https://www.ncbi.nlm.nih.gov/pubmed/23213380 http://dx.doi.org/10.1242/bio.20121115 |
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