Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313888001> ?p ?o ?g. }
- W4313888001 endingPage "770" @default.
- W4313888001 startingPage "759" @default.
- W4313888001 abstract "Mucin4 (MUC4) appears early during pancreatic intraepithelial neoplasia-1 (PanIN1), coinciding with the expression of epidermal growth factor receptor-1 (EGFR). The EGFR signaling is required for the onset of Kras-driven pancreatic ductal adenocarcinoma (PDAC); however, the players and mechanisms involved in sustained EGFR signaling in early PanIN lesions remain elusive. We generated a unique Esai-CRISPR-based Muc4 conditional knockout murine model to evaluate its effect on PDAC pathology. The Muc4 depletion in the autochthonous murine model carrying K-ras and p53 mutations (K-rasG12D; TP53R172H; Pdx-1cre, KPC) to generate the KPCM4−/− murine model showed a significant delay in the PanIN lesion formation with a significant reduction (p < 0.01) in EGFR (Y1068) and ERK1/2 (T202/Y204) phosphorylation. Further, a significant decrease (p < 0.01) in Sox9 expression in PanIN lesions of KPCM4−/− mice suggested the impairment of acinar-to-ductal metaplasia in Muc4-depleted cells. The biochemical analyses demonstrated that MUC4, through its juxtamembrane EGF-like domains, interacts with the EGFR ectodomain, and its cytoplasmic tail prevents EGFR ubiquitination and subsequent proteasomal degradation upon ligand stimulation, leading to sustained downstream oncogenic signaling. Targeting the MUC4 and EGFR interacting interface provides a promising strategy to improve the efficacy of EGFR-targeted therapies in PDAC and other MUC4-expressing malignancies." @default.
- W4313888001 created "2023-01-10" @default.
- W4313888001 creator A5002662464 @default.
- W4313888001 creator A5004120220 @default.
- W4313888001 creator A5005328949 @default.
- W4313888001 creator A5010440741 @default.
- W4313888001 creator A5011108068 @default.
- W4313888001 creator A5014572856 @default.
- W4313888001 creator A5017358599 @default.
- W4313888001 creator A5037086401 @default.
- W4313888001 creator A5039090834 @default.
- W4313888001 creator A5051970161 @default.
- W4313888001 creator A5064299031 @default.
- W4313888001 creator A5069222648 @default.
- W4313888001 creator A5072324344 @default.
- W4313888001 creator A5085256777 @default.
- W4313888001 creator A5086534465 @default.
- W4313888001 creator A5090154787 @default.
- W4313888001 date "2023-01-09" @default.
- W4313888001 modified "2023-10-17" @default.
- W4313888001 title "Muc4 loss mitigates epidermal growth factor receptor activity essential for PDAC tumorigenesis" @default.
- W4313888001 cites W1482687321 @default.
- W4313888001 cites W1509191294 @default.
- W4313888001 cites W1773289659 @default.
- W4313888001 cites W1965462878 @default.
- W4313888001 cites W1969201526 @default.
- W4313888001 cites W1993913862 @default.
- W4313888001 cites W1999289094 @default.
- W4313888001 cites W2018143149 @default.
- W4313888001 cites W2024502310 @default.
- W4313888001 cites W2027877482 @default.
- W4313888001 cites W2035275726 @default.
- W4313888001 cites W2038033248 @default.
- W4313888001 cites W2040775084 @default.
- W4313888001 cites W2043497705 @default.
- W4313888001 cites W2066135299 @default.
- W4313888001 cites W2067407293 @default.
- W4313888001 cites W2067634655 @default.
- W4313888001 cites W2068110593 @default.
- W4313888001 cites W2071607446 @default.
- W4313888001 cites W2076211055 @default.
- W4313888001 cites W2083728982 @default.
- W4313888001 cites W2094252120 @default.
- W4313888001 cites W2106812445 @default.
- W4313888001 cites W2114024778 @default.
- W4313888001 cites W2115247117 @default.
- W4313888001 cites W2117895755 @default.
- W4313888001 cites W2129140055 @default.
- W4313888001 cites W2136214127 @default.
- W4313888001 cites W2150312232 @default.
- W4313888001 cites W2152214346 @default.
- W4313888001 cites W2153359367 @default.
- W4313888001 cites W2157739976 @default.
- W4313888001 cites W2297256877 @default.
- W4313888001 cites W2406860897 @default.
- W4313888001 cites W2500461344 @default.
- W4313888001 cites W2593410994 @default.
- W4313888001 cites W2610190286 @default.
- W4313888001 cites W2614850398 @default.
- W4313888001 cites W2763690609 @default.
- W4313888001 cites W2765838089 @default.
- W4313888001 cites W2777434339 @default.
- W4313888001 cites W2795125785 @default.
- W4313888001 cites W2806062710 @default.
- W4313888001 cites W2909703266 @default.
- W4313888001 cites W2947548345 @default.
- W4313888001 cites W2953013607 @default.
- W4313888001 cites W2969238338 @default.
- W4313888001 cites W3009560356 @default.
- W4313888001 cites W3097468386 @default.
- W4313888001 cites W3141635963 @default.
- W4313888001 cites W3199847019 @default.
- W4313888001 cites W4220915851 @default.
- W4313888001 cites W4226161742 @default.
- W4313888001 cites W4251919186 @default.
- W4313888001 doi "https://doi.org/10.1038/s41388-022-02587-1" @default.
- W4313888001 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36624189" @default.
- W4313888001 hasPublicationYear "2023" @default.
- W4313888001 type Work @default.
- W4313888001 citedByCount "2" @default.
- W4313888001 countsByYear W43138880012023 @default.
- W4313888001 crossrefType "journal-article" @default.
- W4313888001 hasAuthorship W4313888001A5002662464 @default.
- W4313888001 hasAuthorship W4313888001A5004120220 @default.
- W4313888001 hasAuthorship W4313888001A5005328949 @default.
- W4313888001 hasAuthorship W4313888001A5010440741 @default.
- W4313888001 hasAuthorship W4313888001A5011108068 @default.
- W4313888001 hasAuthorship W4313888001A5014572856 @default.
- W4313888001 hasAuthorship W4313888001A5017358599 @default.
- W4313888001 hasAuthorship W4313888001A5037086401 @default.
- W4313888001 hasAuthorship W4313888001A5039090834 @default.
- W4313888001 hasAuthorship W4313888001A5051970161 @default.
- W4313888001 hasAuthorship W4313888001A5064299031 @default.
- W4313888001 hasAuthorship W4313888001A5069222648 @default.
- W4313888001 hasAuthorship W4313888001A5072324344 @default.
- W4313888001 hasAuthorship W4313888001A5085256777 @default.
- W4313888001 hasAuthorship W4313888001A5086534465 @default.
- W4313888001 hasAuthorship W4313888001A5090154787 @default.