Oncogenic KRAS mutation confers chemoresistance by upregulating SIRT1 in non-small cell lung cancer.

ABSTRACT: Kirsten rat sarcoma viral oncogene homologue (KRAS) is a frequent oncogenic driver of solid tumors, including non-small cell lung cancer (NSCLC). The treatment and outcomes of KRAS-mutant cancers have not been dramatically revolutionized by direct KRAS-targeted therapies because of the lack of deep binding pockets for specific small molecule inhibitors. Here, we demonstrated that the mRNA and protein levels of the class III histone deacetylase SIRT1 were upregulated by the KRAS^Mut-Raf-MEK-c-Myc axis in KRAS^Mut lung cancer cells and in lung tumors of a mouse model with spontaneous Kras^G12D expression. KRAS^Mut-induced SIRT1 bound to KRAS^Mut and stably deacetylated KRAS^Mut at lysine 104, which increased KRAS^Mut activ

SUBMITTER: Shin DH 

PROVIDER: S-EPMC10618295 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature