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Noncanonical hedgehog pathway activation through SRF–MKL1 promotes drug resistance in basal cell carcinomas
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https://doi.org/10.1038/nm.4476Abstract
A large proportion of basal cell carcinomas develop resistance independently of the canonical mutations in genes encoding hedgehog pathway components. An unbiased analysis investigating alternative pathways of resistance uncovers the role of cytoskeletal signaling in driving noncanonical activation of hedgehog signaling through nuclear translocation of SRF and MKL1. These results advance understanding of the mechanisms underlying drug resistance and provide new actionable insights for clinical translation.
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