EphA2 promotes the transcription of KLF4 to facilitate stemness in oral squamous cell carcinoma.

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  • Additional Information
    • Source:
      Publisher: Springer Country of Publication: Switzerland NLM ID: 9705402 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-9071 (Electronic) Linking ISSN: 1420682X NLM ISO Abbreviation: Cell Mol Life Sci Subsets: MEDLINE
    • Publication Information:
      Publication: Basel : Springer
      Original Publication: Basel ; Boston : Birkhauser, c1997-
    • Subject Terms:
      Kruppel-Like Factor 4*/metabolism ; Receptor, EphA2*/metabolism ; Receptor, EphA2*/genetics ; Kruppel-Like Transcription Factors*/metabolism ; Kruppel-Like Transcription Factors*/genetics ; Neoplastic Stem Cells*/metabolism ; Neoplastic Stem Cells*/pathology ; Mouth Neoplasms*/pathology ; Mouth Neoplasms*/metabolism ; Mouth Neoplasms*/genetics ; Carcinoma, Squamous Cell*/pathology ; Carcinoma, Squamous Cell*/metabolism ; Carcinoma, Squamous Cell*/genetics; Humans ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Transcription Factors/metabolism ; Transcription Factors/genetics ; Female ; Mice, Nude ; Male ; Prognosis ; MAP Kinase Signaling System/genetics ; Transcription, Genetic
    • Abstract:
      Ephrin receptor A2 (EphA2), a member of the Ephrin receptor family, is closely related to the progression of oral squamous cell carcinoma (OSCC). Cancer stem cells (CSCs) play essential roles in OSCC development and occurrence. The underlying mechanisms between EphA2 and CSCs, however, are not yet fully understood. Here, we found that EphA2 was overexpressed in OSCC tissues and was associated with poor prognosis. Knockdown of EphA2 dampened the CSC phenotype and the tumour-initiating frequency of OSCC cells. Crucially, the effects of EphA2 on the CSC phenotype relied on KLF4, a key transcription factor for CSCs. Mechanistically, EphA2 activated the ERK signalling pathway, promoting the nuclear translocation of YAP. Subsequently, YAP was bound to TEAD3, leading to the transcription of KLF4. Overall, our findings revealed that EphA2 can enhance the stemness of OSCC cells, and this study identified the EphA2/KLF4 axis as a potential target for treating OSCC.
      (© 2024. The Author(s).)
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    • Grant Information:
      82373093 National Natural Science Foundation of China; 82273306 National Natural Science Foundation of China
    • Contributed Indexing:
      Keywords: Cancer stem cells; EphA2; KLF4; OSCC; YAP
    • Accession Number:
      0 (Kruppel-Like Factor 4)
      0 (KLF4 protein, human)
      EC 2.7.10.1 (Receptor, EphA2)
      0 (Kruppel-Like Transcription Factors)
      0 (EPHA2 protein, human)
      0 (Klf4 protein, mouse)
      0 (Transcription Factors)
    • Publication Date:
      Date Created: 20240625 Date Completed: 20240625 Latest Revision: 20240822
    • Publication Date:
      20240822
    • Accession Number:
      PMC11335203
    • Accession Number:
      10.1007/s00018-024-05325-w
    • Accession Number:
      38916835