Noncanonical Wnt/Ror2 signaling regulates cell-matrix crosstalk to prompt directional tumor cell invasion and dissemination in breast cancer
bioRxiv (Cold Spring Harbor Laboratory)(2021)
摘要
Bidirectional cell-extracellular matrix (ECM) interactions represent fundamental exchanges during tumor progression. We demonstrate the noncanonical Wnt receptor, Ror2, regulates tumor cell-driven matrix remodeling in models of breast cancer. Wnt/Ror2 loss-of-function triggers tumor cell invasion, accompanied by changes in actin cytoskeleton, adhesion, and collagen crosslinking gene expression programs. E-cadherin levels decline upon Ror2 depletion, and spatially, we pinpoint the upregulation and redistribution of α5 and β3 integrins together with the production of fibronectin in areas of invasion. Wnt/β-catenin-dependent and Wnt/Ror2 alternative Wnt signaling appear to regulate distinct functions for tumor cells regarding their ability to modify cell-ECM exchanges during invasion. Furthermore, blocking either integrin or focal adhesion kinase (FAK), a downstream mediator of integrin-mediated signal transduction, abrogates the enhanced migration observed upon Ror2 loss. These results reveal a critical function for the alternative Wnt receptor, Ror2, as a determinant of reciprocal communication between tumor cells and ECM during cancer invasion and metastasis.
### Competing Interest Statement
The authors have declared no competing interest.
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关键词
directional tumor cell-matrix invasion,breast cancer,wnt/ror2,non-canonical
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