Laminin-integrin a6b4 interaction activates notch signaling to facilitate bladder cancer development
Abstract 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 developme...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-022-09645-7 |
| _version_ | 1818549685048049664 |
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| author | Nan Hao Daming Yang Tianpei Liu Shucheng Liu Xinsheng Lu Libo Chen |
| author_facet | Nan Hao Daming Yang Tianpei Liu Shucheng Liu Xinsheng Lu Libo Chen |
| author_sort | Nan Hao |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-12T08:36:34Z |
| format | Article |
| id | doaj.art-05bdfd8c16e54b07a46d974c009f0858 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-12T08:36:34Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-05bdfd8c16e54b07a46d974c009f08582022-12-22T00:30:54ZengBMCBMC Cancer1471-24072022-05-0122111110.1186/s12885-022-09645-7Laminin-integrin a6b4 interaction activates notch signaling to facilitate bladder cancer developmentNan Hao0Daming Yang1Tianpei Liu2Shucheng Liu3Xinsheng Lu4Libo Chen5Department of Urology, the People’s Hospital of Guangxi Zhuang Autonomous RegionDepartment of Urology, the People’s Hospital of Guangxi Zhuang Autonomous RegionDepartment of Urology, the First Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Urology, the First Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Urology, the First Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Urology, the First Affiliated Hospital, Hengyang Medical School, University of South ChinaAbstract 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.https://doi.org/10.1186/s12885-022-09645-7LamininNotch signalingBladder cancerIntegrins |
| spellingShingle | Nan Hao Daming Yang Tianpei Liu Shucheng Liu Xinsheng Lu Libo Chen Laminin-integrin a6b4 interaction activates notch signaling to facilitate bladder cancer development BMC Cancer Laminin Notch signaling Bladder cancer Integrins |
| 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 | Laminin Notch signaling Bladder cancer Integrins |
| url | https://doi.org/10.1186/s12885-022-09645-7 |
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