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Suppression of PPARGC1A causes collateral sensitivity to HMGCR-inhibitor within BRAFi-treatement resistant melanoma

ABSTRACT: We aimed to identify the potential proteins as a collateral vulnerability within PGC1a-suppressed BRAF-inhibitor resistant melanomas, and the potential mechanisms behind this including their abundancy and cellular distribution.

INSTRUMENT(S): Orbitrap Eclipse, Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Melanocyte

DISEASE(S): Melanoma And Neural System Tumor Syndrome

SUBMITTER: Haopeng Xiao

LAB HEAD: Pere Puigserver

PROVIDER: PXD041952 | Pride | 2023-06-09

REPOSITORIES: Pride

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Epigenetic suppression of PGC1α (PPARGC1A) causes collateral sensitivity to HMGCR-inhibitors within BRAF-treatment resistant melanomas.

Liang Jiaxin J Yu Deyang D Luo Chi C Bennett Christopher C Jedrychowski Mark M Gygi Steve P SP Widlund Hans R HR Puigserver Pere P

Nature communications 20230605 1

While targeted treatment against BRAF(V600E) improve survival for melanoma patients, many will see their cancer recur. Here we provide data indicating that epigenetic suppression of PGC1α defines an aggressive subset of chronic BRAF-inhibitor treated melanomas. A metabolism-centered pharmacological screen further identifies statins (HMGCR inhibitors) as a collateral vulnerability within PGC1α-suppressed BRAF-inhibitor resistant melanomas. Lower PGC1α levels mechanistically causes reduced RAB6B a ...[more]

PMID: 37277330

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