FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3036458210> ?p ?o ?g. }

• W3036458210 abstract "Ligand-dependent activation of Hedgehog (Hh) signaling in cancer occurs without mutations in canonical pathway genes. Consequently, the genetic basis of Hh pathway activation in adult solid tumors, such as small-cell lung cancer (SCLC), is unknown. Here we show that combined inactivation of Trp53 and Rb1, a defining genetic feature of SCLC, leads to hypersensitivity to Hh ligand in vitro, and during neural tube development in vivo. This response is associated with the aberrant formation of primary cilia, an organelle essential for canonical Hh signaling through smoothened, a transmembrane protein targeted by small-molecule Hh inhibitors. We further show that loss of both Trp53 and Rb1 disables transcription of genes in the autophagic machinery necessary for the degradation of primary cilia. In turn, we also demonstrate a requirement for Kif3a, a gene essential for the formation of primary cilia, in a mouse model of SCLC induced by conditional deletion of both Trp53 and Rb1 in the adult airway. Our results provide a mechanistic framework for therapeutic targeting of ligand-dependent Hh signaling in human cancers with somatic mutations in both TP53 and RB1." @default.
• W3036458210 created "2020-06-25" @default.
• W3036458210 creator A5002588324 @default.
• W3036458210 creator A5006102759 @default.
• W3036458210 creator A5012795226 @default.
• W3036458210 creator A5020706368 @default.
• W3036458210 creator A5039774562 @default.
• W3036458210 creator A5043907665 @default.
• W3036458210 creator A5052652340 @default.
• W3036458210 creator A5056260786 @default.
• W3036458210 creator A5060601077 @default.
• W3036458210 creator A5066009774 @default.
• W3036458210 creator A5079399767 @default.
• W3036458210 date "2020-06-22" @default.
• W3036458210 modified "2023-10-03" @default.
• W3036458210 title "Trp53 and Rb1 regulate autophagy and ligand-dependent Hedgehog signaling" @default.
• W3036458210 cites W1527759415 @default.
• W3036458210 cites W1538926863 @default.
• W3036458210 cites W1761323037 @default.
• W3036458210 cites W1903523058 @default.
• W3036458210 cites W1966818564 @default.
• W3036458210 cites W1969370465 @default.
• W3036458210 cites W1978286483 @default.
• W3036458210 cites W1984999562 @default.
• W3036458210 cites W1990138203 @default.
• W3036458210 cites W1994772304 @default.
• W3036458210 cites W1996743997 @default.
• W3036458210 cites W1999532278 @default.
• W3036458210 cites W2003302159 @default.
• W3036458210 cites W2003383185 @default.
• W3036458210 cites W2012712609 @default.
• W3036458210 cites W2023028445 @default.
• W3036458210 cites W2027146979 @default.
• W3036458210 cites W2029327556 @default.
• W3036458210 cites W2030199762 @default.
• W3036458210 cites W2030430693 @default.
• W3036458210 cites W2034132952 @default.
• W3036458210 cites W2034962229 @default.
• W3036458210 cites W2042461504 @default.
• W3036458210 cites W2048132571 @default.
• W3036458210 cites W2055296003 @default.
• W3036458210 cites W2059499603 @default.
• W3036458210 cites W2070632651 @default.
• W3036458210 cites W2075994912 @default.
• W3036458210 cites W2079525834 @default.
• W3036458210 cites W2084424168 @default.
• W3036458210 cites W2091684557 @default.
• W3036458210 cites W2097803027 @default.
• W3036458210 cites W2104892374 @default.
• W3036458210 cites W2114333899 @default.
• W3036458210 cites W2146731647 @default.
• W3036458210 cites W2151199834 @default.
• W3036458210 cites W2151607263 @default.
• W3036458210 cites W2153889566 @default.
• W3036458210 cites W2515857015 @default.
• W3036458210 cites W2554199252 @default.
• W3036458210 cites W2624613535 @default.
• W3036458210 cites W2624809039 @default.
• W3036458210 cites W2625887862 @default.
• W3036458210 cites W2748137738 @default.
• W3036458210 cites W2792662781 @default.
• W3036458210 cites W2803554589 @default.
• W3036458210 cites W2803961608 @default.
• W3036458210 doi "https://doi.org/10.1172/jci132513" @default.
• W3036458210 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7410056" @default.
• W3036458210 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32568216" @default.
• W3036458210 hasPublicationYear "2020" @default.
• W3036458210 type Work @default.
• W3036458210 sameAs 3036458210 @default.
• W3036458210 citedByCount "7" @default.
• W3036458210 countsByYear W30364582102020 @default.
• W3036458210 countsByYear W30364582102021 @default.
• W3036458210 countsByYear W30364582102022 @default.
• W3036458210 countsByYear W30364582102023 @default.
• W3036458210 crossrefType "journal-article" @default.
• W3036458210 hasAuthorship W3036458210A5002588324 @default.
• W3036458210 hasAuthorship W3036458210A5006102759 @default.
• W3036458210 hasAuthorship W3036458210A5012795226 @default.
• W3036458210 hasAuthorship W3036458210A5020706368 @default.
• W3036458210 hasAuthorship W3036458210A5039774562 @default.
• W3036458210 hasAuthorship W3036458210A5043907665 @default.
• W3036458210 hasAuthorship W3036458210A5052652340 @default.
• W3036458210 hasAuthorship W3036458210A5056260786 @default.
• W3036458210 hasAuthorship W3036458210A5060601077 @default.
• W3036458210 hasAuthorship W3036458210A5066009774 @default.
• W3036458210 hasAuthorship W3036458210A5079399767 @default.
• W3036458210 hasBestOaLocation W30364582101 @default.
• W3036458210 hasConcept C100094513 @default.
• W3036458210 hasConcept C145837895 @default.
• W3036458210 hasConcept C170493617 @default.
• W3036458210 hasConcept C24530287 @default.
• W3036458210 hasConcept C2778539099 @default.
• W3036458210 hasConcept C502942594 @default.
• W3036458210 hasConcept C54355233 @default.
• W3036458210 hasConcept C62478195 @default.
• W3036458210 hasConcept C86803240 @default.
• W3036458210 hasConcept C88498014 @default.
• W3036458210 hasConcept C95444343 @default.
• W3036458210 hasConceptScore W3036458210C100094513 @default.
• W3036458210 hasConceptScore W3036458210C145837895 @default.

• next