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Laminin-integrin a6b4 interaction activates notch signaling to facilitate bladder cancer development
BACKGROUND: Laminins are high-molecular weight (400 ~ 900 kDa) proteins in extracellular matrix, which serve as major component of the basal lamina, and play a crucial role in promoting tumor cell migration. This study aimed at characterizing the role of laminin in promoting cancer development, and...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118635/ https://www.ncbi.nlm.nih.gov/pubmed/35585515 http://dx.doi.org/10.1186/s12885-022-09645-7 |
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author | Hao, Nan Yang, Daming Liu, Tianpei Liu, Shucheng Lu, Xinsheng Chen, Libo |
author_facet | Hao, Nan Yang, Daming Liu, Tianpei Liu, Shucheng Lu, Xinsheng Chen, Libo |
author_sort | Hao, Nan |
collection | PubMed |
description | BACKGROUND: Laminins are high-molecular weight (400 ~ 900 kDa) proteins in extracellular matrix, which serve as major component of the basal lamina, and play a crucial role in promoting tumor cell migration. This study aimed at characterizing the role of laminin in promoting cancer development, and elucidating the mechanism of tumor progression driven by laminin-Notch signaling in bladder cancer. METHODS: 2D collagen/laminin culture system was established and CCK-8/transwell assay was conducted to evaluate the proliferation/migration ability of Biu-87 and MB49 cells cultured on 2D gels. Activation of integrins-Notch1 signaling was determined by western blotting. Orthotopic bladder cancer mice model was established to assess the therapeutic effects of Notch inhibitor. RESULTS: Our study demonstrated that extracellular laminin can trigger tumor cell proliferation/migration through integrin α6β4/Notch1 signaling in bladder cancer. Inhibition of Telomere repeat-binding factor 3 (TRB3)/Jagged Canonical Notch Ligand 1 (JAG1) signaling suppressed Notch signals activation induced by laminin-integrin axis. In MB49 orthotopic bladder cancer mice model, Notch inhibitor SAHM1 efficiently improved tumor suppressive effects of chemotherapy and prolonged survival time of tumor-bearing mice. CONCLUSION: In conclusion, we show that, in bladder cancer, extracellular laminin induced the activation of Notch pathway through integrin α6β4/TRB3/JAG3, and disclosed a novel role of laminin in bladder cancer cells proliferation or migration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09645-7. |
format | Online Article Text |
id | pubmed-9118635 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-91186352022-05-20 Laminin-integrin a6b4 interaction activates notch signaling to facilitate bladder cancer development Hao, Nan Yang, Daming Liu, Tianpei Liu, Shucheng Lu, Xinsheng Chen, Libo BMC Cancer Research BACKGROUND: Laminins are high-molecular weight (400 ~ 900 kDa) proteins in extracellular matrix, which serve as major component of the basal lamina, and play a crucial role in promoting tumor cell migration. This study aimed at characterizing the role of laminin in promoting cancer development, and elucidating the mechanism of tumor progression driven by laminin-Notch signaling in bladder cancer. METHODS: 2D collagen/laminin culture system was established and CCK-8/transwell assay was conducted to evaluate the proliferation/migration ability of Biu-87 and MB49 cells cultured on 2D gels. Activation of integrins-Notch1 signaling was determined by western blotting. Orthotopic bladder cancer mice model was established to assess the therapeutic effects of Notch inhibitor. RESULTS: Our study demonstrated that extracellular laminin can trigger tumor cell proliferation/migration through integrin α6β4/Notch1 signaling in bladder cancer. Inhibition of Telomere repeat-binding factor 3 (TRB3)/Jagged Canonical Notch Ligand 1 (JAG1) signaling suppressed Notch signals activation induced by laminin-integrin axis. In MB49 orthotopic bladder cancer mice model, Notch inhibitor SAHM1 efficiently improved tumor suppressive effects of chemotherapy and prolonged survival time of tumor-bearing mice. CONCLUSION: In conclusion, we show that, in bladder cancer, extracellular laminin induced the activation of Notch pathway through integrin α6β4/TRB3/JAG3, and disclosed a novel role of laminin in bladder cancer cells proliferation or migration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09645-7. BioMed Central 2022-05-18 /pmc/articles/PMC9118635/ /pubmed/35585515 http://dx.doi.org/10.1186/s12885-022-09645-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Hao, Nan Yang, Daming Liu, Tianpei Liu, Shucheng Lu, Xinsheng Chen, Libo Laminin-integrin a6b4 interaction activates notch signaling to facilitate bladder cancer development |
title | Laminin-integrin a6b4 interaction activates notch signaling to facilitate bladder cancer development |
title_full | Laminin-integrin a6b4 interaction activates notch signaling to facilitate bladder cancer development |
title_fullStr | Laminin-integrin a6b4 interaction activates notch signaling to facilitate bladder cancer development |
title_full_unstemmed | Laminin-integrin a6b4 interaction activates notch signaling to facilitate bladder cancer development |
title_short | Laminin-integrin a6b4 interaction activates notch signaling to facilitate bladder cancer development |
title_sort | laminin-integrin a6b4 interaction activates notch signaling to facilitate bladder cancer development |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118635/ https://www.ncbi.nlm.nih.gov/pubmed/35585515 http://dx.doi.org/10.1186/s12885-022-09645-7 |
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