FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387235548> ?p ?o ?g. }

• W4387235548 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 KRASMut-Raf-MEK-c-Myc axis in KRASMut lung cancer cells and in lung tumors of a mouse model with spontaneous KrasG12D expression. KRASMut-induced SIRT1 bound to KRASMut and stably deacetylated KRASMut at lysine 104, which increased KRASMut activity. SIRT1 knockdown (K/D) or the SIRT1H363Y mutation increased KRASMut acetylation, which decreased KRASMut activity and sensitized tumors to the anticancer effects of cisplatin and erlotinib. Furthermore, in KrasG12D/+;Sirt1co/co mice, treatment with cisplatin and erlotinib robustly reduced the tumor burden and increased survival rates compared with those in spontaneous LSL-KrasG12D/+;Sirt1+/+ mice and mice in each single-drug treatment group. Then, we identified p300 as a KRASMut acetyltransferase that reinforced KRASMut lysine 104 acetylation and robustly decreased KRASMut activity. KRASMut lysine 104 acetylation by p300 and deacetylation by SIRT1 were confirmed by LC‒MS/MS. Consistent with this finding, the SIRT1 inhibitor EX527 suppressed KRASMut activity, which synergistically abolished cell proliferation and colony formation, as well as the tumor burden in KRASMut mice, when combined with cisplatin or erlotinib. Our data reveal a novel pathway critical for the regulation of KRASMut lung cancer progression and provide important evidence for the potential application of SIRT1 inhibitors and p300 activators for the combination treatment of KRASMut lung cancer patients." @default.
• W4387235548 created "2023-10-02" @default.
• W4387235548 creator A5015102949 @default.
• W4387235548 creator A5019282015 @default.
• W4387235548 creator A5032497606 @default.
• W4387235548 creator A5055387346 @default.
• W4387235548 creator A5060866107 @default.
• W4387235548 creator A5068023720 @default.
• W4387235548 date "2023-10-02" @default.
• W4387235548 modified "2023-10-12" @default.
• W4387235548 title "Oncogenic KRAS mutation confers chemoresistance by upregulating SIRT1 in non-small cell lung cancer" @default.
• W4387235548 cites W1722289295 @default.
• W4387235548 cites W1757407923 @default.
• W4387235548 cites W1775236918 @default.
• W4387235548 cites W1979376000 @default.
• W4387235548 cites W1983166456 @default.
• W4387235548 cites W1984073962 @default.
• W4387235548 cites W1987065605 @default.
• W4387235548 cites W1989857875 @default.
• W4387235548 cites W1991746961 @default.
• W4387235548 cites W1992072826 @default.
• W4387235548 cites W1992207445 @default.
• W4387235548 cites W1994772304 @default.
• W4387235548 cites W2010312807 @default.
• W4387235548 cites W2010658012 @default.
• W4387235548 cites W2011376105 @default.
• W4387235548 cites W2012157460 @default.
• W4387235548 cites W2015022497 @default.
• W4387235548 cites W2019106516 @default.
• W4387235548 cites W2022631487 @default.
• W4387235548 cites W2027146979 @default.
• W4387235548 cites W2031909580 @default.
• W4387235548 cites W2037475133 @default.
• W4387235548 cites W2037723157 @default.
• W4387235548 cites W2043361335 @default.
• W4387235548 cites W2049662137 @default.
• W4387235548 cites W2060768223 @default.
• W4387235548 cites W2061593125 @default.
• W4387235548 cites W2066605494 @default.
• W4387235548 cites W2070739037 @default.
• W4387235548 cites W2071754840 @default.
• W4387235548 cites W2074343204 @default.
• W4387235548 cites W2081990599 @default.
• W4387235548 cites W2083695927 @default.
• W4387235548 cites W2089350319 @default.
• W4387235548 cites W2091437677 @default.
• W4387235548 cites W2096173332 @default.
• W4387235548 cites W2096882254 @default.
• W4387235548 cites W2103130163 @default.
• W4387235548 cites W2112078762 @default.
• W4387235548 cites W2113782651 @default.
• W4387235548 cites W2114288614 @default.
• W4387235548 cites W2128059540 @default.
• W4387235548 cites W2128339707 @default.
• W4387235548 cites W2131152510 @default.
• W4387235548 cites W2133362776 @default.
• W4387235548 cites W2134630203 @default.
• W4387235548 cites W2135184154 @default.
• W4387235548 cites W2135242575 @default.
• W4387235548 cites W2136882950 @default.
• W4387235548 cites W2138383559 @default.
• W4387235548 cites W2140925956 @default.
• W4387235548 cites W2146236962 @default.
• W4387235548 cites W2158797467 @default.
• W4387235548 cites W2168889003 @default.
• W4387235548 cites W2171236206 @default.
• W4387235548 cites W2172236291 @default.
• W4387235548 cites W2182482244 @default.
• W4387235548 cites W2234281493 @default.
• W4387235548 cites W2412945422 @default.
• W4387235548 cites W2423433037 @default.
• W4387235548 cites W2580767461 @default.
• W4387235548 cites W2581362192 @default.
• W4387235548 cites W2765656723 @default.
• W4387235548 cites W2884531362 @default.
• W4387235548 cites W2895923466 @default.
• W4387235548 cites W2994071131 @default.
• W4387235548 cites W2998581726 @default.
• W4387235548 cites W3090224263 @default.
• W4387235548 cites W3093903224 @default.
• W4387235548 cites W3127567089 @default.
• W4387235548 cites W3130115867 @default.
• W4387235548 cites W3135859755 @default.
• W4387235548 cites W3155376330 @default.
• W4387235548 cites W4205148275 @default.
• W4387235548 cites W4225876587 @default.
• W4387235548 cites W4249713142 @default.
• W4387235548 cites W4293176077 @default.
• W4387235548 cites W650890981 @default.
• W4387235548 doi "https://doi.org/10.1038/s12276-023-01091-0" @default.
• W4387235548 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37779142" @default.
• W4387235548 hasPublicationYear "2023" @default.
• W4387235548 type Work @default.
• W4387235548 citedByCount "0" @default.
• W4387235548 crossrefType "journal-article" @default.
• W4387235548 hasAuthorship W4387235548A5015102949 @default.
• W4387235548 hasAuthorship W4387235548A5019282015 @default.
• W4387235548 hasAuthorship W4387235548A5032497606 @default.
• W4387235548 hasAuthorship W4387235548A5055387346 @default.
• W4387235548 hasAuthorship W4387235548A5060866107 @default.

• next