The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Smoothened Variants Explain the Majority of Drug Resistance in Basal Cell Carcinoma
Open accessAbstract
Advanced basal cell carcinomas (BCCs) frequently acquire resistance to Smoothened (SMO) inhibitors through unknown mechanisms. Here we identify SMO mutations in 50% (22 of 44) of resistant BCCs and show that these mutations maintain Hedgehog signaling in the presence of SMO inhibitors. Alterations include four ligand binding pocket mutations defining sites of inhibitor binding and four variants conferring constitutive activity and inhibitor resistance, illuminating pivotal residues that ensure receptor autoinhibition. In the presence of a SMO inhibitor, tumor cells containing either class of SMO mutants effectively outcompete cells containing the wild-type SMO. Finally, we show that both classes of SMO variants respond to aPKC-ι/λ or GLI2 inhibitors that operate downstream of SMO, setting the stage for the clinical use of GLI antagonists.
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Cites
Mapping and quantifying mammalian transcriptomes by RNA-Seq
Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L., & Wold, B. (2008) · Nature Methods · doi:10.1038/nmeth.1226 · Cited by 13,696
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Self-citationGenomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma
Bonilla, X., Parmentier, L., King, B., Bezrukov, F., Kaya, G., Zoete, V., Seplyarskiy, V. B., Sharpe, H. J., McKee, T., Letourneau, A., et al. (2016) · Nature Genetics · doi:10.1038/ng.3525 · Cited by 490
Pietrobono, S., Gagliardi, S., & Stecca, B. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00556 · Cited by 303
A slow-cycling LGR5 tumour population mediates basal cell carcinoma relapse after therapy
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G protein–coupled receptors control the sensitivity of cells to the morphogen Sonic Hedgehog
Pusapati, G. V., Kong, J. H., Patel, B. B., Gouti, M., Sagner, A., Sircar, R., Luchetti, G., Ingham, P. W., Briscoe, J., & Rohatgi, R. (2018) · Science Signaling · doi:10.1126/scisignal.aao5749 · Cited by 91
Metadata
- Authors
- Atwood, S. X., Sarin, K. Y., Whitson, R. J., Li, J. R., Kim, G., Rezaee, M., Ally, M. S., Kim, J., Yao, C., Chang, A. L. S., Oro, A. E., & Tang, J. Y.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 27
- Issue
- 3
- Pages
- 342-353
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2108444995
- Cited by
- 404
- References
- 1
- FWCI
- 18.01
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Atwood, S. X., Sarin, K. Y., Whitson, R. J., Li, J. R., Kim, G., Rezaee, M., Ally, M. S., Kim, J., Yao, C., Chang, A. L. S., Oro, A. E., & Tang, J. Y. (2015). Smoothened Variants Explain the Majority of Drug Resistance in Basal Cell Carcinoma. Cancer Cell. https://doi.org/10.1016/j.ccell.2015.02.002
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