Tenascin-C promotes tumor cell migration and metastasis through integrin {alpha}9{beta}1 -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 remain 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. 

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