MTOR promotes basal cell carcinoma growth through atypical PKC

Autor: Rachel Y. Chow, Daniel P. Cedeno, Scott X. Atwood, Taylor M. Levee, Linda Doan, Gurleen Kaur
Rok vydání: 2020
Předmět:
0301 basic medicine
Skin Neoplasms
Basal Cell
Biochemistry
Mice
030207 dermatology & venereal diseases
0302 clinical medicine
skin and connective tissue diseases
Protein Kinase C
Cancer
Tumor
integumentary system
Triazines
Chemistry
TOR Serine-Threonine Kinases
Imidazoles
SMO antagonist
Immunohistochemistry
Hedgehog signaling pathway
Patched-1 Receptor
cancer therapy
Sequence Analysis
Atypical pkc
Signal Transduction
medicine.drug
animal structures
Clinical Sciences
Antineoplastic Agents
Dermatology
cancer heterogeneity
Zinc Finger Protein GLI1
Article
Cell Line
03 medical and health sciences
Cell Line
Tumor
medicine
Animals
Humans
Tumor growth
Hedgehog Proteins
Basal cell carcinoma
Everolimus
Molecular Biology
Hedgehog
PI3K/AKT/mTOR pathway
Cell Proliferation
Sirolimus
drug resistance
Sequence Analysis
RNA
Cell growth
Dermatology & Venereal Diseases
Carcinoma
fungi
medicine.disease
030104 developmental biology
PTCH1
Carcinoma
Basal Cell
Hedgehog signalling
Cancer research
RNA
Immunostaining
Zdroj: Exp Dermatol
Experimental dermatology, vol 30, iss 3
ISSN: 1600-0625
0906-6705
DOI: 10.1111/exd.14255
Popis: 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 ofPtch1fl/fl;Gli1-CreERT2mice 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.
Databáze: OpenAIRE
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