ETV5 facilitates tumor progression in head-neck squamous cell carcinoma.

Publisher: Munksgaard Country of Publication: Denmark NLM ID: 9508565 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1601-0825 (Electronic) Linking ISSN: 1354523X NLM ISO Abbreviation: Oral Dis Subsets: MEDLINE

Publication: 2001- : Copenhagen, Denmark : Munksgaard
Original Publication: Houndmills, Basingstoke, Hampshire, UK : Stockton Press, c1995-

Squamous Cell Carcinoma of Head and Neck*/genetics ; Squamous Cell Carcinoma of Head and Neck*/pathology ; Squamous Cell Carcinoma of Head and Neck*/metabolism ; Transcription Factors*/genetics ; Transcription Factors*/metabolism ; Head and Neck Neoplasms*/genetics ; Head and Neck Neoplasms*/metabolism ; Head and Neck Neoplasms*/pathology ; Disease Progression* ; DNA-Binding Proteins*/genetics ; DNA-Binding Proteins*/metabolism ; Cell Proliferation*/genetics; Humans ; Animals ; Male ; Cell Line, Tumor ; Female ; Mice ; Snail Family Transcription Factors/metabolism ; Snail Family Transcription Factors/genetics ; Apoptosis/genetics ; Cell Movement/genetics ; Middle Aged ; Mice, Nude ; Neoplasm Invasiveness/genetics ; Promoter Regions, Genetic/genetics ; Gene Expression Regulation, Neoplastic

Objective: E26 transformation-specific (ETS) factors have emerged as key mediators underlying human tumorigenesis. Here, we sought to characterize the expression pattern, biological roles, and clinical significance of ETS Variant Transcription Factor 5 (ETV5) in head neck squamous cell carcinoma (HNSCC).
Subjects and Methods: ETV5 expression pattern in HNSCC was determined by bioinformatics interrogations and immunohistochemical staining in primary samples. The associations between its abundance with clinicopathological parameters, and patient survival were evaluated. Colony formation, CCK-8, flow cytometry, wound healing, and Transwell invasion assays, as well as xenograft models, were utilized to determine the phenotypic changes after ETV5 silencing in vitro and vivo. The potential binding of ETV5 in the Slug promoter was determined by ChIP-qPCR.
Results: ETV5 was significantly overexpressed in HNSCC samples. Its overexpression is significantly associated with aggressiveness features and reduced survival. ETV5 knockdown significantly inhibited cell proliferation, migration, invasion, and induced apoptosis in vitro, and impaired tumor growth in vivo. Moreover, ETV5-activated Slug transcription by binding its promoter region in HNSCC cells. Patients with ETV5 ^high Slug ^high had the worst survival across multiple HNSCC cohorts.
Conclusions: Our findings reveal that ETV5 serves as a novel prognostic biomarker and putative oncogene for HNSCC progression likely by activating Slug transcription.
(© 2023 Wiley Periodicals LLC.)

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Key Research Program in Jiangsu Province-Social Developmental Project; National Natural Science Foundation of China; Research program from Jiangsu Commission of Health; the Priority Academic Program Development of Jiangsu Higher Education Institutions

Keywords: ETV5; head neck squamous cell carcinoma; prognostic biomarker; slug

0 (ETV5 protein, human)
0 (Transcription Factors)
0 (DNA-Binding Proteins)
0 (Snail Family Transcription Factors)
0 (SNAI1 protein, human)

Date Created: 20230831 Date Completed: 20240531 Latest Revision: 20240703

20240703

10.1111/odi.14724

37649213