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Autor(en) / Beteiligte
Titel
IDENTIFICATION OF MUC1-C AS A TARGET FOR SUPPRESSING PROGRESSION OF HEAD AND NECK SQUAMOUS CELL CARCINOMAS
Ist Teil von
  • Cancer research communications, 2024-05, Vol.4 (5), p.1268-1281
Ort / Verlag
United States: American Association for Cancer Research
Erscheinungsjahr
2024
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
  • The MUC1-C protein is aberrantly expressed in adenocarcinomas of epithelial barrier tissues and contributes to their progression. Less is known about involvement of MUC1-C in the pathogenesis of squamous cell carcinomas (SCCs). Here, we report that the MUC1 gene is upregulated in advanced head and neck SCCs (HNSCCs). Studies of HNSCC cell lines demonstrate that the MUC1-C subunit regulates expression of (i) RIG-I and MDA5 pattern recognition receptors, (ii) STAT1 and interferon (IFN) regulatory factors, and (iii) downstream IFN-stimulated genes (ISGs). MUC1-C integrates chronic activation of the STAT1 inflammatory pathway with induction of the ∆Np63 and SOX2 genes that are aberrantly expressed in HNSCCs. In extending those dependencies, we demonstrate that MUC1-C is necessary for NOTCH3 expression, self-renewal capacity and tumorigenicity. The findings that MUC1 associates with ∆Np63, SOX2 and NOTCH3 expression by scRNA-seq analysis further indicate that MUC1-C drives the HNSCC stem cell state and is a target for suppressing HNSCC progression.
Sprache
Englisch
Identifikatoren
eISSN: 2767-9764
DOI: 10.1158/2767-9764.CRC-24-0011
Titel-ID: cdi_proquest_miscellaneous_3039236782

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