2. Academic Validation
  3. EphA2 promotes the transcription of KLF4 to facilitate stemness in oral squamous cell carcinoma

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

  • Cell Mol Life Sci. 2024 Jun 25;81(1):278. doi: 10.1007/s00018-024-05325-w.
Junqiang Bai # 1,  Yang Chen # 1 2,  Yunqing Sun 1,  Xinmiao Wang 1,  Yifan Wang 1,  Shutian Guo 1,  Zhengjun Shang 3 4,  Zhe Shao 5 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
  • 2 Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
  • 3 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. shangzhengjun@whu.edu.cn.
  • 4 Department of Oral and Maxillofacial-Head and Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. shangzhengjun@whu.edu.cn.
  • 5 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. shaozhe@whu.edu.cn.
  • 6 Day Surgery Center, School and Hospital of Stomatology, Wuhan University, Wuhan, China. shaozhe@whu.edu.cn.
  • # Contributed equally.
PMID: 38916835 DOI: 10.1007/s00018-024-05325-w
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.

Keywords

Cancer stem cells; EphA2; KLF4; OSCC; YAP.

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