Loss of CDKN2A remodels Golgi morphology to create a lipid peroxidation vulnerability

CDKN2A/p16-Low melanoma cells show a Golgi-compaction phenotype that creates heightened vulnerability to pharmacologic Golgi disruption via lipid peroxidation.

• Why it matters: Therapies that selectively target tumors with complete or reduced CDKN2A/p16 expression are lacking, leaving an unmet need to find actionable vulnerabilities in CDKN2A/p16-Low cancers.
• What they did: A CRISPR knockout screen in melanoma cells identified Golgi membrane–associated genes as essential for CDKN2A/p16-Low survival, and CDKN2A/p16 knockdown caused striking Golgi compaction.
• The result: CDKN2A/p16 knockdown sensitized cells to lipid-peroxidation–linked Golgi disruption both in vitro and in vivo, and reduced RB1 expression did not reproduce the sensitivity.

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