Transcriptomics

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New compounds triggering endoplasmic reticulum stress exert anti-melanoma effects and overcome BRAF inhibitor resistance


ABSTRACT: We discovered and developed a new series of molecules (thiazole benzenesulfonamides). HA15, the lead compound of this series, displayed anti-cancerous activity on all tested melanoma cells including those isolated from patients and those that developed resistance to BRAF inhibitors. Our molecule displayed activity against other liquid and solid tumors. HA15 also exhibited strong efficacy in xenograft mouse models with melanoma cells either sensitive or resistant to BRAF inhibitors. Transcriptomic, proteomic and biochemical studies identified the chaperone BiP/GRP78/HSPA5 as the specific target of HA15 and demonstrated that the interaction increases endoplasmic reticulum (ER) stress, leading to melanoma cell death by concomitant induction of autophagic and apoptotic mechanisms.

ORGANISM(S): Homo sapiens

PROVIDER: GSE79071 | GEO | 2016/06/01

SECONDARY ACCESSION(S): PRJNA314870

REPOSITORIES: GEO

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