WNK1 promotes head and neck squamous cell carcinoma progression through activation of NF-κB signaling pathway

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Publicat a:Discover Oncology vol. 16, no. 1 (Dec 2025), p. 1822
Autor principal: Chen, Ru-zhen
Altres autors: Li, Rui, Cheng, Bing-lin, Lu, Si-bei, Hu, Wen, Lin, Feng, Wen, Xin, Chen, Yue, Wang, Ying-lei, Zhang, Mo-ting, Hong, Xiao-hong, Tang, Xin-ran
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Springer Nature B.V.
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Accés en línia:Citation/Abstract
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022 |a 1868-8500 
024 7 |a 10.1007/s12672-025-03637-2  |2 doi 
035 |a 3257698744 
045 2 |b d20251201  |b d20251231 
100 1 |a Chen, Ru-zhen  |u Southern Medical University, Department of Radiation Oncology, Nanfang Hospital, Guangzhou, China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471) 
245 1 |a WNK1 promotes head and neck squamous cell carcinoma progression through activation of NF-κB signaling pathway 
260 |b Springer Nature B.V.  |c Dec 2025 
513 |a Journal Article 
520 3 |a BackgroundRecurrence and metastasis represent the primary causes of therapeutic failure in head and neck squamous cell carcinoma (HNSCC). However, the underlying molecular mechanisms driving these processes remain incompletely elucidated.MethodsWNK1 (with-no-lysine kinase 1) expression in both normal and HNSCC tissues was analyzed using the TCGA, TIMER2.0 and Clinical Proteomic Tumor Analysis Consortium (CPTAC) datasets, and further validated in HNSCC cell lines by Western blot. Cell Counting Kit-8 (CCK-8), colony formation, Transwell, and orthotopic xenograft assays were conducted to assess the biological role of WNK1 in HNSCC proliferation and metastasis. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) -based quantitative proteomics and post-translational modification profiling were performed to explore the underlying molecular mechanisms.ResultsWNK1 overexpression was significantly elevated in HNSCC tissues and cell lines and was correlated with reduced overall survival. WNK1 knockdown suppressed tumor growth and metastasis both in vivo and in vitro. Proteomic and phosphoproteomic profiling of WNK1-driven alterations identified critical signaling pathways closely associated with tumor malignancy. Specifically, WNK1 promotes NF-κB activation through RELA (p65) phosphorylation and nuclear accumulation, resulting in the upregulation of pro-tumorigenic effectors.ConclusionsElevated WNK1 drives invasive progression and distant metastasis in HNSCC through NF-κB-dependent transcriptional reprogramming, highlighting its potential as a novel therapeutic target for HNSCC. 
610 4 |a Food & Drug Administration--FDA 
653 |a Cancer 
653 |a Medical prognosis 
653 |a Metastasis 
653 |a Squamous cell carcinoma 
653 |a Genomes 
653 |a Phosphorylation 
653 |a Tumors 
653 |a Genes 
653 |a Human papillomavirus 
653 |a Cell growth 
653 |a Kinases 
653 |a Protein expression 
653 |a Comparative analysis 
653 |a Proteins 
700 1 |a Li, Rui  |u Southern Medical University, Department of Radiation Oncology, Nanfang Hospital, Guangzhou, China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471) 
700 1 |a Cheng, Bing-lin  |u Southern Medical University, Department of Radiation Oncology, Nanfang Hospital, Guangzhou, China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471) 
700 1 |a Lu, Si-bei  |u Southern Medical University, The First School of Clinical Medicine, Guangzhou, China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471) 
700 1 |a Hu, Wen  |u Southern Medical University, Department of Radiation Oncology, Nanfang Hospital, Guangzhou, China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471) 
700 1 |a Lin, Feng  |u Southern Medical University, Department of Radiation Oncology, Nanfang Hospital, Guangzhou, China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471) 
700 1 |a Wen, Xin  |u Southern Medical University, Department of Radiation Oncology, Nanfang Hospital, Guangzhou, China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471) 
700 1 |a Chen, Yue  |u Southern Medical University, Department of Radiation Oncology, Nanfang Hospital, Guangzhou, China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471) 
700 1 |a Wang, Ying-lei  |u Southern Medical University, The First School of Clinical Medicine, Guangzhou, China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471) 
700 1 |a Zhang, Mo-ting  |u Southern Medical University, The First School of Clinical Medicine, Guangzhou, China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471) 
700 1 |a Hong, Xiao-hong  |u Southern Medical University, Department of Radiation Oncology, Nanfang Hospital, Guangzhou, China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471) 
700 1 |a Tang, Xin-ran  |u Southern Medical University, Department of Radiation Oncology, Nanfang Hospital, Guangzhou, China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471) 
773 0 |t Discover Oncology  |g vol. 16, no. 1 (Dec 2025), p. 1822 
786 0 |d ProQuest  |t Health & Medical Collection 
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