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bioRxiv · 10.1101/2021.05.15.444295

Non-canonical Wnt/Ror2 signaling status regulates cell-matrix crosstalk to prompt directional tumor cell invasion and dissemination in breast cancer

Si, H.·Zhao, N.·Pedroza, A.·Creighton, C. J.·Roarty, K.
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Abstract

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 5 and {beta}3 integrins together with the production of fibronectin in areas of invasion. Wnt/{beta}-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.

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Si, H., Zhao, N., Pedroza, A., Creighton, C. J., Roarty, K.. 2021-05-16. Non-canonical Wnt/Ror2 signaling status regulates cell-matrix crosstalk to prompt directional tumor cell invasion and dissemination in breast cancer. https://doi.org/10.1101/2021.05.15.444295

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