Selective abrogation of S6K2 identifies lipid homeostasis as a survival vulnerability in MAPK inhibitor-resistant NRAS-mutant melanoma.

doi:10.1126/scitranslmed.adp8913

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Article

Selective abrogation of S6K2 identifies lipid homeostasis as a survival vulnerability in MAPK inhibitor-resistant NRAS-mutant melanoma.

Science translational medicine - 5 Feb 2025

Lipchick Brittany, Guterres Adam N, Chen Hsin-Yi, Zundell Delaine M, Del Aguila Segundo, Reyes-Uribe Patricia I, Tirado Yulissa, Basu Subhasree, Yin Xiangfan, Kossenkov Andrew V, Lu Yiling, Mills Gordon B, Liu Qin, Goldman Aaron R, Murphy Maureen E, Speicher David W, Villanueva Jessie

Abstract excerpt

Although oncogenic NRAS activates mitogen-activated protein kinase (MAPK) signaling, inhibition of the MAPK pathway is not therapeutically efficacious in NRAS-mutant (NRASMUT) tumors. Here, we report that selectively silencing the ribosomal protein S6 kinase 2 (S6K2) while preserving the activity of S6K1 perturbs lipid metabolism, enhances fatty acid unsaturation, and triggers lethal lipid peroxidation in NRASMUT...

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Topics

Melanoma
Animals
Humans
Drug Resistance, Neoplasm
Cell Line, Tumor

Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

Lipid Metabolism

Homeostasis

GTP Phosphohydrolases

Mutation

Mice

Protein Kinase Inhibitors

Membrane Proteins

Mitogen-Activated Protein Kinases

Endoplasmic Reticulum Stress

Cell Survival

Xenograft Model Antitumor Assays

Source

Open in PubMed Open full text

Identifiers

PMID: 39908352
DOI: 10.1126/scitranslmed.adp8913
PMCID: PMC12258192

Genes

NRAS

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 22 Oct 2026.

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