New data shows that as dermal fibroblasts grow old, they increase their secretion of the Wnt antagonist sFRP2 to drive melanoma cell metastasis. sFRP2 suppresses β-catenin and MITF signaling in melanoma cells, downregulating the redox regulator APE1, making melanoma cells more sensitive to oxidative stress and driving resistance to BRAF inhibitors. Thus, the aging microenvironment in elderly patient skin activates a signaling pathway that drives more aggressive melanoma cell behavior.
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