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N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma.

Sofia GeroyskaIsabel MejiaAlfred A ChanMarian NavarreteVijaya PandeySamuel KharpatinJuliana NogutiFeng WangDaniel N SroleTsui-Fen ChouJames Akira WohlschlegelElizabeta NemethRobert DamoiseauxDavid B ShackelfordDelphine J LeeBegoña Díaz
Published in: Cancer research communications (2024)
KRAS-mutant lung carcinomas with LKB1 and/or KEAP1 co-mutations have intrinsic therapeutic resistance. We show that these tumors are sensitive to NMT inhibitors, which slow tumor growth in vivo and sensitize cells to platinum-based chemotherapy in vitro. Inhibition of myristoylation causes death by parthanatos and thus has the potential to kill apoptosis and ferroptosis-resistant cancer cells. Our findings warrant investigation of NMT as a therapeutic target in highly aggressive lung carcinomas.
Keyphrases
  • cell cycle arrest
  • cell death
  • oxidative stress
  • induced apoptosis
  • endoplasmic reticulum stress
  • wild type
  • squamous cell carcinoma
  • pi k akt
  • locally advanced
  • signaling pathway
  • human health