Journal
CANCER RESEARCH
Volume 78, Issue 4, Pages 950-961Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-17-1597
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Funding
- Worldwide Cancer Research [14-1070]
- INSERM
- University Strasbourg
- ANR (AngioMatrix)
- INCa
- Ligue contre le Cancer
- Chinese Scholarship Council
- Fondation ARC, Association pour la recherche sur le cancer
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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 micro-environment. In a murine xenograft model of advanced human osteosarcoma, tenascin-C and its receptor integrin alpha 9 beta 1 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 sig-nature 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. Significance: These results illuminate how the extracellular matrix glycoprotein tenascin-C in the tumor microenvironment promotes invasive migration and metastatic progression by employing integrin alpha 9 beta 1, abolishing actin stress fiber formation, inhibiting YAP and its target gene expression, with potential implications for cancer prognosis and therapy. (C) 2017 AACR.
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