Matches in SemOpenAlex for { <https://semopenalex.org/work/W4317502646> ?p ?o ?g. }
- W4317502646 endingPage "245" @default.
- W4317502646 startingPage "232" @default.
- W4317502646 abstract "NOTCH1 mutant clones occupy the majority of normal human esophagus by middle age but are comparatively rare in esophageal cancers, suggesting NOTCH1 mutations drive clonal expansion but impede carcinogenesis. Here we test this hypothesis. Sequencing NOTCH1 mutant clones in aging human esophagus reveals frequent biallelic mutations that block NOTCH1 signaling. In mouse esophagus, heterozygous Notch1 mutation confers a competitive advantage over wild-type cells, an effect enhanced by loss of the second allele. Widespread Notch1 loss alters transcription but has minimal effects on the epithelial structure and cell dynamics. In a carcinogenesis model, Notch1 mutations were less prevalent in tumors than normal epithelium. Deletion of Notch1 reduced tumor growth, an effect recapitulated by anti-NOTCH1 antibody treatment. Notch1 null tumors showed reduced proliferation. We conclude that Notch1 mutations in normal epithelium are beneficial as wild-type Notch1 favors tumor expansion. NOTCH1 blockade may have therapeutic potential in preventing esophageal squamous cancer." @default.
- W4317502646 created "2023-01-20" @default.
- W4317502646 creator A5005354262 @default.
- W4317502646 creator A5018279248 @default.
- W4317502646 creator A5019231020 @default.
- W4317502646 creator A5026295052 @default.
- W4317502646 creator A5027490511 @default.
- W4317502646 creator A5032702053 @default.
- W4317502646 creator A5034174069 @default.
- W4317502646 creator A5038826533 @default.
- W4317502646 creator A5039116074 @default.
- W4317502646 creator A5039267119 @default.
- W4317502646 creator A5077153702 @default.
- W4317502646 creator A5082522262 @default.
- W4317502646 creator A5084427833 @default.
- W4317502646 date "2023-01-19" @default.
- W4317502646 modified "2023-10-14" @default.
- W4317502646 title "Notch1 mutations drive clonal expansion in normal esophageal epithelium but impair tumor growth" @default.
- W4317502646 cites W1956871134 @default.
- W4317502646 cites W1967658333 @default.
- W4317502646 cites W1979812265 @default.
- W4317502646 cites W2004346548 @default.
- W4317502646 cites W2021114160 @default.
- W4317502646 cites W2023490488 @default.
- W4317502646 cites W2044168765 @default.
- W4317502646 cites W2048049362 @default.
- W4317502646 cites W2062917229 @default.
- W4317502646 cites W2067131315 @default.
- W4317502646 cites W2068511866 @default.
- W4317502646 cites W2085021251 @default.
- W4317502646 cites W2099059205 @default.
- W4317502646 cites W2103118693 @default.
- W4317502646 cites W2113337076 @default.
- W4317502646 cites W2143726980 @default.
- W4317502646 cites W2152711806 @default.
- W4317502646 cites W2172204402 @default.
- W4317502646 cites W2172258358 @default.
- W4317502646 cites W2342789489 @default.
- W4317502646 cites W2419558864 @default.
- W4317502646 cites W2513121575 @default.
- W4317502646 cites W2524881570 @default.
- W4317502646 cites W2570401594 @default.
- W4317502646 cites W2611387862 @default.
- W4317502646 cites W2612650514 @default.
- W4317502646 cites W2767653410 @default.
- W4317502646 cites W2768561639 @default.
- W4317502646 cites W2779538387 @default.
- W4317502646 cites W2892348456 @default.
- W4317502646 cites W2893107001 @default.
- W4317502646 cites W2894045715 @default.
- W4317502646 cites W2894486342 @default.
- W4317502646 cites W2897064819 @default.
- W4317502646 cites W2898789672 @default.
- W4317502646 cites W2905667684 @default.
- W4317502646 cites W2949177718 @default.
- W4317502646 cites W2957792958 @default.
- W4317502646 cites W2958645511 @default.
- W4317502646 cites W3011179310 @default.
- W4317502646 cites W3025298198 @default.
- W4317502646 cites W3094507538 @default.
- W4317502646 cites W3160369250 @default.
- W4317502646 cites W3165875563 @default.
- W4317502646 cites W3207879702 @default.
- W4317502646 doi "https://doi.org/10.1038/s41588-022-01280-z" @default.
- W4317502646 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36658434" @default.
- W4317502646 hasPublicationYear "2023" @default.
- W4317502646 type Work @default.
- W4317502646 citedByCount "10" @default.
- W4317502646 countsByYear W43175026462023 @default.
- W4317502646 crossrefType "journal-article" @default.
- W4317502646 hasAuthorship W4317502646A5005354262 @default.
- W4317502646 hasAuthorship W4317502646A5018279248 @default.
- W4317502646 hasAuthorship W4317502646A5019231020 @default.
- W4317502646 hasAuthorship W4317502646A5026295052 @default.
- W4317502646 hasAuthorship W4317502646A5027490511 @default.
- W4317502646 hasAuthorship W4317502646A5032702053 @default.
- W4317502646 hasAuthorship W4317502646A5034174069 @default.
- W4317502646 hasAuthorship W4317502646A5038826533 @default.
- W4317502646 hasAuthorship W4317502646A5039116074 @default.
- W4317502646 hasAuthorship W4317502646A5039267119 @default.
- W4317502646 hasAuthorship W4317502646A5077153702 @default.
- W4317502646 hasAuthorship W4317502646A5082522262 @default.
- W4317502646 hasAuthorship W4317502646A5084427833 @default.
- W4317502646 hasBestOaLocation W43175026461 @default.
- W4317502646 hasConcept C104317684 @default.
- W4317502646 hasConcept C105702510 @default.
- W4317502646 hasConcept C121608353 @default.
- W4317502646 hasConcept C143065580 @default.
- W4317502646 hasConcept C1491633281 @default.
- W4317502646 hasConcept C180754005 @default.
- W4317502646 hasConcept C2777819096 @default.
- W4317502646 hasConcept C501734568 @default.
- W4317502646 hasConcept C502942594 @default.
- W4317502646 hasConcept C529295009 @default.
- W4317502646 hasConcept C54355233 @default.
- W4317502646 hasConcept C555283112 @default.
- W4317502646 hasConcept C57708383 @default.
- W4317502646 hasConcept C62112901 @default.