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Integrin-independent support of cancer drug resistance by tetraspanin CD151

Tetraspanin protein CD151 has typically been studied as binding partner and functional regulator of laminin-binding integrins. However, we show here that CD151 supports anti-cancer drug resistance independent of integrins. CD151 ablation sensitized multiple tumor cell types to several anti-cancer dr...

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Autores principales: Hwang, Soonyean, Takimoto, Takayuki, Hemler, Martin E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439156/
https://www.ncbi.nlm.nih.gov/pubmed/30778617
http://dx.doi.org/10.1007/s00018-019-03014-7
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author Hwang, Soonyean
Takimoto, Takayuki
Hemler, Martin E.
author_facet Hwang, Soonyean
Takimoto, Takayuki
Hemler, Martin E.
author_sort Hwang, Soonyean
collection PubMed
description Tetraspanin protein CD151 has typically been studied as binding partner and functional regulator of laminin-binding integrins. However, we show here that CD151 supports anti-cancer drug resistance independent of integrins. CD151 ablation sensitized multiple tumor cell types to several anti-cancer drugs (e.g., gefitinib and camptothecin), thus increasing apoptosis, as seen using cleaved caspase-3, cleaved PARP (poly (ADP-ribose) polymerase), annexin V, and propidium iodide staining assays. Drug sensitization due to CD151 ablation is integrin-independent, because, (1) effects occurred in cells when integrins were unengaged with ligand, (2) integrin ablation (α3 and α6 subunits) did not mimic effects of CD151 ablation, (3) the CD151(QRD) mutant, with diminished integrin association, and CD151(WT) (unmutated CD151) similarly reconstituted drug protection, and (4) treatment with anti-cancer drugs selectively upregulated intracellular nonintegrin-associated CD151 (NIA-CD151), consistent with its role in drug resistance. Together, these results suggest that upregulated CD151 expression may support not only typical integrin-dependent functions, but also integrin-independent survival of circulating (and possibly metastatic) cancer cells during anti-cancer drug therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00018-019-03014-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-64391562019-04-15 Integrin-independent support of cancer drug resistance by tetraspanin CD151 Hwang, Soonyean Takimoto, Takayuki Hemler, Martin E. Cell Mol Life Sci Original Article Tetraspanin protein CD151 has typically been studied as binding partner and functional regulator of laminin-binding integrins. However, we show here that CD151 supports anti-cancer drug resistance independent of integrins. CD151 ablation sensitized multiple tumor cell types to several anti-cancer drugs (e.g., gefitinib and camptothecin), thus increasing apoptosis, as seen using cleaved caspase-3, cleaved PARP (poly (ADP-ribose) polymerase), annexin V, and propidium iodide staining assays. Drug sensitization due to CD151 ablation is integrin-independent, because, (1) effects occurred in cells when integrins were unengaged with ligand, (2) integrin ablation (α3 and α6 subunits) did not mimic effects of CD151 ablation, (3) the CD151(QRD) mutant, with diminished integrin association, and CD151(WT) (unmutated CD151) similarly reconstituted drug protection, and (4) treatment with anti-cancer drugs selectively upregulated intracellular nonintegrin-associated CD151 (NIA-CD151), consistent with its role in drug resistance. Together, these results suggest that upregulated CD151 expression may support not only typical integrin-dependent functions, but also integrin-independent survival of circulating (and possibly metastatic) cancer cells during anti-cancer drug therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00018-019-03014-7) contains supplementary material, which is available to authorized users. Springer International Publishing 2019-02-18 2019 /pmc/articles/PMC6439156/ /pubmed/30778617 http://dx.doi.org/10.1007/s00018-019-03014-7 Text en © The Author(s) 2019 OpenAccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Hwang, Soonyean
Takimoto, Takayuki
Hemler, Martin E.
Integrin-independent support of cancer drug resistance by tetraspanin CD151
title Integrin-independent support of cancer drug resistance by tetraspanin CD151
title_full Integrin-independent support of cancer drug resistance by tetraspanin CD151
title_fullStr Integrin-independent support of cancer drug resistance by tetraspanin CD151
title_full_unstemmed Integrin-independent support of cancer drug resistance by tetraspanin CD151
title_short Integrin-independent support of cancer drug resistance by tetraspanin CD151
title_sort integrin-independent support of cancer drug resistance by tetraspanin cd151
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439156/
https://www.ncbi.nlm.nih.gov/pubmed/30778617
http://dx.doi.org/10.1007/s00018-019-03014-7
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