Premium
MTOR promotes basal cell carcinoma growth through atypical PKC
Author(s) -
Chow Rachel Y.,
Levee Taylor M.,
Kaur Gurleen,
Cedeno Daniel P.,
Doan Linda T.,
Atwood Scott X.
Publication year - 2021
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.14255
Subject(s) - pi3k/akt/mtor pathway , hedgehog signaling pathway , gli1 , cancer research , basal cell carcinoma , biology , everolimus , sirolimus , hedgehog , cell growth , ptch1 , smoothened , phosphorylation , immunostaining , microbiology and biotechnology , signal transduction , medicine , immunohistochemistry , immunology , basal cell , biochemistry , genetics
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 for patients with advanced or metastatic BCC. Here, we use a combination of RNA‐sequencing analysis of advanced human BCC tumor–normal pairs and immunostaining of human and mouse BCC samples to identify an MTOR expression signature in BCC. Pharmacological inhibition of MTOR activity in BCC cells significantly reduces cell proliferation without affecting HH signalling. Similarly, treatment of the Ptch1 fl / fl ; Gli1 ‐ Cre ERT2 mouse BCC tumor model with everolimus reduces tumor growth. aPKC, a downstream target of MTOR, shows reduced activity, suggesting that MTOR promotes tumor growth by activating aPKC and demonstrating that suppressing MTOR could be a promising target for BCC patients.