Tenascin-C Promotes Tumor Cell Migration and Metastasis through Integrin α9β1-Mediated YAP Inhibition.

ABSTRACT: 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 i

SUBMITTER: Sun Z 

PROVIDER: S-EPMC5901716 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature