The membrane protein Smoothened (SMO) is an oncogenic effector of Hedgehog (HH) signalling and is a drug target for cancers such as basal-cell carcinomas (BCCs), but resistance mutations in SMO have emerged. From a proteomics screen to search for additional HH pathway components as alternative drug targets, Atwood et al. found the polarity protein atypical protein kinase Cι/λ (aPKCι/λ), and they showed that it acts downstream of SMO in the activation of the GLI1 transcription factor. An inhibitor of aPKCι/λ suppressed both the growth of therapy-naive allografted BCCs in mice and also the proliferation of SMO-inhibitor-resistant BCC cells in vitro.
ORIGINAL RESEARCH PAPER
Atwood, S. X. et al. GLI activation by atypical protein kinase Cι/λ regulates the growth of basal cell carcinomas. Nature 494, 484–488 (2013)
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Burgess, D. A smooth alternative?. Nat Rev Cancer 13, 221 (2013). https://doi.org/10.1038/nrc3504
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DOI: https://doi.org/10.1038/nrc3504