Matches in SemOpenAlex for { <https://semopenalex.org/work/W4384696088> ?p ?o ?g. }
- W4384696088 abstract "Abstract Peutz-Jeghers syndrome (PJS) is a familial disorder caused by heterozygous inactivating Liver Kinase B1 ( LKB1) mutations that promote gastrointestinal polyposis and enhance cancer susceptibility. How LKB1 -deficiency alters the phenotypical landscape and hierarchical organization of epithelial tissues to mediate increased cancer risk remains poorly understood. Here, we employ small intestinal organoids to investigate these issues for heterozygous and homozygous Lkb1 epithelial loss. We show that Lkb1 loss causes an allele dosage-dependent activation of a transcriptional program for tissue repair that is already induced in stem cell populations and mediates alterations in secretory cell type morphology and positioning. Furthermore, this shift towards a regenerative state omits the need for EGF supplementation, thus inducing niche-independent properties. Strikingly, we uncover that heterozygous loss of Lkb1 is sufficient to push the epithelium into a premalignant program for colorectal carcinogenesis along the serrated pathway, which is further amplified by loss-of-heterozygosity (LOH) or Kras mutations. We conclude that persistent upregulation of a regenerative program due to LKB1 loss alters cellular hierarchy and induces niche independency, which predisposes PJS epithelium to uncontrolled growth along the serrated pathway." @default.
- W4384696088 created "2023-07-20" @default.
- W4384696088 creator A5009367933 @default.
- W4384696088 creator A5016487295 @default.
- W4384696088 creator A5017100786 @default.
- W4384696088 creator A5018673682 @default.
- W4384696088 creator A5027327386 @default.
- W4384696088 creator A5028640805 @default.
- W4384696088 creator A5030871402 @default.
- W4384696088 creator A5035007676 @default.
- W4384696088 creator A5036565670 @default.
- W4384696088 creator A5044269827 @default.
- W4384696088 creator A5044273874 @default.
- W4384696088 creator A5047711039 @default.
- W4384696088 creator A5061768197 @default.
- W4384696088 creator A5068068698 @default.
- W4384696088 creator A5071483953 @default.
- W4384696088 creator A5085843442 @default.
- W4384696088 creator A5092494116 @default.
- W4384696088 date "2023-07-17" @default.
- W4384696088 modified "2023-09-27" @default.
- W4384696088 title "Intestinal LKB1 loss drives a pre-malignant program along the serrated cancer pathway" @default.
- W4384696088 cites W1619256199 @default.
- W4384696088 cites W1655178001 @default.
- W4384696088 cites W1872124954 @default.
- W4384696088 cites W1965157206 @default.
- W4384696088 cites W1969843034 @default.
- W4384696088 cites W1974883167 @default.
- W4384696088 cites W1976323469 @default.
- W4384696088 cites W1977709885 @default.
- W4384696088 cites W1988903229 @default.
- W4384696088 cites W1997921299 @default.
- W4384696088 cites W1998536076 @default.
- W4384696088 cites W1998563859 @default.
- W4384696088 cites W2001258296 @default.
- W4384696088 cites W2002375694 @default.
- W4384696088 cites W2002513358 @default.
- W4384696088 cites W2019759811 @default.
- W4384696088 cites W2044874695 @default.
- W4384696088 cites W2045129123 @default.
- W4384696088 cites W2046625047 @default.
- W4384696088 cites W2048011978 @default.
- W4384696088 cites W2052498320 @default.
- W4384696088 cites W2054490779 @default.
- W4384696088 cites W2059227275 @default.
- W4384696088 cites W2065260669 @default.
- W4384696088 cites W2067495748 @default.
- W4384696088 cites W2073691821 @default.
- W4384696088 cites W2086313707 @default.
- W4384696088 cites W2091798264 @default.
- W4384696088 cites W2100650216 @default.
- W4384696088 cites W2105256330 @default.
- W4384696088 cites W2106302419 @default.
- W4384696088 cites W2117692326 @default.
- W4384696088 cites W2120207971 @default.
- W4384696088 cites W2125393482 @default.
- W4384696088 cites W2138440877 @default.
- W4384696088 cites W2142011430 @default.
- W4384696088 cites W2154937854 @default.
- W4384696088 cites W2156719841 @default.
- W4384696088 cites W2157010562 @default.
- W4384696088 cites W2159582900 @default.
- W4384696088 cites W2168735820 @default.
- W4384696088 cites W2403475582 @default.
- W4384696088 cites W2526262591 @default.
- W4384696088 cites W2757884195 @default.
- W4384696088 cites W2767423581 @default.
- W4384696088 cites W2771984786 @default.
- W4384696088 cites W2773293509 @default.
- W4384696088 cites W2788560984 @default.
- W4384696088 cites W2793500447 @default.
- W4384696088 cites W2794480084 @default.
- W4384696088 cites W2810563185 @default.
- W4384696088 cites W2883292720 @default.
- W4384696088 cites W2941492678 @default.
- W4384696088 cites W2947852257 @default.
- W4384696088 cites W2950993016 @default.
- W4384696088 cites W2958334035 @default.
- W4384696088 cites W2979482964 @default.
- W4384696088 cites W2985983100 @default.
- W4384696088 cites W2989630635 @default.
- W4384696088 cites W2999107325 @default.
- W4384696088 cites W3119003316 @default.
- W4384696088 cites W3122155574 @default.
- W4384696088 cites W3191116136 @default.
- W4384696088 cites W4200259443 @default.
- W4384696088 cites W4200479208 @default.
- W4384696088 cites W4213026128 @default.
- W4384696088 cites W4246779090 @default.
- W4384696088 cites W4283716873 @default.
- W4384696088 cites W4286250788 @default.
- W4384696088 doi "https://doi.org/10.1101/2023.07.17.548873" @default.
- W4384696088 hasPublicationYear "2023" @default.
- W4384696088 type Work @default.
- W4384696088 citedByCount "0" @default.
- W4384696088 crossrefType "posted-content" @default.
- W4384696088 hasAuthorship W4384696088A5009367933 @default.
- W4384696088 hasAuthorship W4384696088A5016487295 @default.
- W4384696088 hasAuthorship W4384696088A5017100786 @default.
- W4384696088 hasAuthorship W4384696088A5018673682 @default.