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bioRxiv · 10.1101/2020.08.24.264598

MTOR promotes basal cell carcinoma growth through atypical PKC

Chow, R. Y.·Levee, T. M.·Kaur, G.·Cedeno, D. P.·Doan, L. T.·Atwood, S. X.
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Abstract

Advanced basal cell carcinomas (BCCs) are driven by the Hedgehog (HH) pathway and often possess inherent resistance to SMO inhibitors. Identifying and targeting pathways that bypass SMO could provide alternative treatments. Here, we use a combination of RNA-sequencing analysis of advanced BCC tumor-normal pairs and immunostaining of human and mouse BCC samples to identify an MTOR signature in BCC. Pharmacological inhibition of MTOR activity in BCC cells significantly reduces cell proliferation without affecting HH signaling. Similarly, treatment of Ptch1fl/fl; Gli1-CreERT2 mice with everolimus reduces tumor growth and aPKC activity, suggesting that MTOR promotes tumor growth by activating aPKC and demonstrating that suppressing MTOR could be a promising target for BCC patients.

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Chow, R. Y., Levee, T. M., Kaur, G., Cedeno, D. P., Doan, L. T., Atwood, S. X.. 2020-08-24. MTOR promotes basal cell carcinoma growth through atypical PKC. https://doi.org/10.1101/2020.08.24.264598

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