RICTOR Affects Melanoma Tumorigenesis and Its Resistance to Targeted Therapy.

ABSTRACT: The network defined by phosphatidylinositol-3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR) plays a major role in melanoma oncogenesis and has been implicated in BRAF inhibitor resistance. The central role of RICTOR (rapamycin-insensitive companion of mTOR) in this pathway has only recently begun to be unraveled. In the present study, we assessed the role of mTORC2/RICTOR in BRAF-mutated melanomas and their resistance to BRAF inhibition. We showed that RICTOR was significantly overexpressed in melanoma and associated with bad prognoses. RICTOR overexpression stimulated melanoma-initiating cells (MICs) with 'stemness' properties. We also showed that RICTOR contributed to melanoma resistance to BRAF inhibitors and rendered the cells very sensitive to mTORC2 inhibition. We high

SUBMITTER: Jebali A 

PROVIDER: S-EPMC8533235 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature