Tenascin-C promotes tumor cell migration and metastasis through integrin α9β1–mediated YAP inhibition
Tenascin-C is an extracellular matrix molecule that drives progression of many types of human cancer, but the basis for its actions remains obscure. In this study, we describe a cell-autonomous signaling mechanism explaining how tenascin-C promotes cancer cell migration in the tumor microenvironment...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Published: |
American Association for Cancer Research
2017
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| _version_ | 1797103282791907328 |
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| author | Sun, Z Schwenzer, A Rupp, T Murdamoothoo, M Vegliante, R Lefebvre, O Klein, A Hussenet, T Orend, G |
| author_facet | Sun, Z Schwenzer, A Rupp, T Murdamoothoo, M Vegliante, R Lefebvre, O Klein, A Hussenet, T Orend, G |
| author_sort | Sun, Z |
| collection | OXFORD |
| description | Tenascin-C is an extracellular matrix molecule that drives progression of many types of human cancer, but the basis for its actions remains obscure. In this study, we describe a cell-autonomous signaling mechanism explaining how tenascin-C promotes cancer cell migration in the tumor microenvironment. In a murine xenograft model of advanced human osteosarcoma, tenascin-C and its receptor integrin α9β1 were determined to be essential for lung metastasis of tumor cells. We determined that activation of this pathway also reduced tumor cell–autonomous expression of target genes for the transcription factor YAP. In clinical specimens, a genetic signature comprising four YAP target genes represents prognostic impact. Taken together, our results illuminate how tumor cell deposition of tenascin-C in the tumor microenvironment promotes invasive migration and metastatic progression. |
| first_indexed | 2024-03-07T06:17:53Z |
| format | Journal article |
| id | oxford-uuid:f1b6cff9-6345-495b-95dc-d2392c02e02a |
| institution | University of Oxford |
| last_indexed | 2024-03-07T06:17:53Z |
| publishDate | 2017 |
| publisher | American Association for Cancer Research |
| record_format | dspace |
| spelling | oxford-uuid:f1b6cff9-6345-495b-95dc-d2392c02e02a2022-03-27T11:58:07ZTenascin-C promotes tumor cell migration and metastasis through integrin α9β1–mediated YAP inhibitionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f1b6cff9-6345-495b-95dc-d2392c02e02aSymplectic Elements at OxfordAmerican Association for Cancer Research2017Sun, ZSchwenzer, ARupp, TMurdamoothoo, MVegliante, RLefebvre, OKlein, AHussenet, TOrend, GTenascin-C is an extracellular matrix molecule that drives progression of many types of human cancer, but the basis for its actions remains obscure. In this study, we describe a cell-autonomous signaling mechanism explaining how tenascin-C promotes cancer cell migration in the tumor microenvironment. In a murine xenograft model of advanced human osteosarcoma, tenascin-C and its receptor integrin α9β1 were determined to be essential for lung metastasis of tumor cells. We determined that activation of this pathway also reduced tumor cell–autonomous expression of target genes for the transcription factor YAP. In clinical specimens, a genetic signature comprising four YAP target genes represents prognostic impact. Taken together, our results illuminate how tumor cell deposition of tenascin-C in the tumor microenvironment promotes invasive migration and metastatic progression. |
| spellingShingle | Sun, Z Schwenzer, A Rupp, T Murdamoothoo, M Vegliante, R Lefebvre, O Klein, A Hussenet, T Orend, G Tenascin-C promotes tumor cell migration and metastasis through integrin α9β1–mediated YAP inhibition |
| title | Tenascin-C promotes tumor cell migration and metastasis through integrin α9β1–mediated YAP inhibition |
| title_full | Tenascin-C promotes tumor cell migration and metastasis through integrin α9β1–mediated YAP inhibition |
| title_fullStr | Tenascin-C promotes tumor cell migration and metastasis through integrin α9β1–mediated YAP inhibition |
| title_full_unstemmed | Tenascin-C promotes tumor cell migration and metastasis through integrin α9β1–mediated YAP inhibition |
| title_short | Tenascin-C promotes tumor cell migration and metastasis through integrin α9β1–mediated YAP inhibition |
| title_sort | tenascin c promotes tumor cell migration and metastasis through integrin α9β1 mediated yap inhibition |
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