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

التفاصيل البيبلوغرافية
العنوان: EphA2 promotes the transcription of KLF4 to facilitate stemness in oral squamous cell carcinoma.
المؤلفون: Bai J; 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., Chen Y; 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.; Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China., Sun Y; 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., Wang X; 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., Wang Y; 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., Guo S; 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., Shang Z; 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.; Department of Oral and Maxillofacial-Head and Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. shangzhengjun@whu.edu.cn., Shao Z; 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.; Day Surgery Center, School and Hospital of Stomatology, Wuhan University, Wuhan, China. shaozhe@whu.edu.cn.
المصدر: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2024 Jun 25; Vol. 81 (1), pp. 278. Date of Electronic Publication: 2024 Jun 25.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: 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
أسماء مطبوعة: Publication: Basel : Springer
Original Publication: Basel ; Boston : Birkhauser, c1997-
مواضيع طبية MeSH: 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
مستخلص: 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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معلومات مُعتمدة: 82373093 National Natural Science Foundation of China; 82273306 National Natural Science Foundation of China
فهرسة مساهمة: Keywords: Cancer stem cells; EphA2; KLF4; OSCC; YAP
المشرفين على المادة: 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)
تواريخ الأحداث: Date Created: 20240625 Date Completed: 20240625 Latest Revision: 20240715
رمز التحديث: 20240715
DOI: 10.1007/s00018-024-05325-w
PMID: 38916835
قاعدة البيانات: MEDLINE
الوصف
تدمد:1420-9071
DOI:10.1007/s00018-024-05325-w