학술논문

AMBRA1 and FAK1: crosstalking for improved targeted therapy in melanoma
Document Type
article
Source
Molecular & Cellular Oncology, Vol 8, Iss 4 (2021)
Subject
ambra1
fak1
melanoma
metastasis
tumor growth
therapy
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Language
English
ISSN
2372-3556
23723556
Abstract
Through genetically engineered mouse models of melanoma, we identified Autophagy/beclin 1 regulator 1 (Ambra1) as novel tumor-suppressor in melanoma. In these settings, loss of Ambra1 associated with the hyperactivation of focal adhesion kinase 1 (Fak1) signaling, the inhibition of which resulted in reduced tumor growth and invasiveness. We therefore propose FAK1 inhibition for current melanoma therapy in AMBRA1-low tumors. Abbreviations AKT, serine/threonine kinase 1; AMBRA1, autophagy/beclin 1 regulator 1; BRAF, v-raf murine sarcoma viral oncogene homolog; BRAFi, BRAF inhibitor; CCLE, Cancer Cell Line Encyclopedia;g ESTDAB, European Searchable Tumor Line Database; FAK1, focal adhesion kinase 1; FAKi, FAK1 inhibitor; LMC, Leeds Melanoma Cohort; MEK, MAPK/ERK kinase; PP2A, protein phosphatase 2A; PTEN, phosphatase and tensin homolog; TCGA-SKCM, The Cancer Genome Atlas - Skin Cutaneous Melanoma; YAP, yes-associated protein 1.