ArticleCell death and differentiation2023
Inhibition of USP14 promotes TNFα-induced cell death in head and neck squamous cell carcinoma (HNSCC).
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 31 citations in OpenAlex.
- USP14 promotes head and neck squamous cell carcinoma progression via deubiquitinating and stabilizing CFL2.Future science OA · 2026Article
- Emerging regulatory model of Ubiquitin-Specific Proteases 14 in cancer: from canonical oncogenesis to TME modulation, therapeutic resistance, and non-canonical activities.Journal of translational medicine · 2026Review
- Targeting USP14 enhances immunotherapy response by reprogramming tumor-associated macrophages in colon cancer.iScience · 2026Article
- b-AP15 enhances TRAIL-induced cell death in HNSCC via the induction of ROS/JNK/DR5 signalling.Cancer gene therapy · 2026Article
- USP14 promotes epithelial-mesenchymal transition and functions as a multifaceted biomarker in lung adenocarcinoma.Discover oncology · 2026Article
- Ubiquitin-centered post-translational modification crosstalk orchestrates tumor immunity and immunotherapy response.Experimental hematology & oncology · 2026Review
- Biomimetic carbon nanopolymers ANM-NPs act on mannose receptors and complement receptors to promote tumor antigen presentation.Journal for immunotherapy of cancer · 2025Article
- USP14-mediated stabilization of ACTN1 maintains mesenchymal characteristics in glioblastoma.Communications biology · 2025Article
- WNK1 promotes head and neck squamous cell carcinoma progression through activation of NF-κB signaling pathway.Discover oncology · 2025Article
- Decoding the ubiquitin network: molecular mechanisms and therapeutic vulnerabilities for precision radio-sensitization in cancer.Molecular cancer · 2025Review
- USP14 Mediates Molecular Mechanisms Regulating Aortic Valve Stenosis Through Ubiquitination.Journal of cellular and molecular medicine · 2025Article
- USP14 and UCHL5 synergistically deubiquitinate PKCα and translocate NF-κB to promote the progression of anaplastic thyroid cancer.Cell death & disease · 2025Article
- USP14 targets FABP5-mediated ferroptosis to promote proliferation and cisplatin resistance of HNSCC.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Targeting the TRIM14/USP14 axis enhances radiotherapy efficacy by inducing GPX4 degradation and disrupting ferroptotic defense in HCC.Cell death & disease · 2025Article
- Review
- N4BP3 Activates TLR4-NF-κB Pathway in Inflammatory Bowel Disease by Promoting K48-Linked IκBα Ubiquitination.Journal of inflammation research · 2025Article
- Implication of protein post translational modifications in gastric cancer.Frontiers in cell and developmental biology · 2025Review
- Decoding microbial carcinogenic strategies: ubiquitination and SUMO modification.Frontiers in microbiology · 2025Review
- Functional RNAi Screening Identifies G2/M and Kinetochore Components as Modulators of TNFα/NF-κB Prosurvival Signaling in Head and Neck Squamous Cell Carcinoma.Cancer research communications · 2024Article
- E7-mediated repression of miR-203 promotes LASP1-dependent proliferation in HPV-positive cervical cancer.Oncogene · 2024Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 2 countries.
Funding
Abstract
TNFα is a key mediator of immune, chemotherapy and radiotherapy-induced cytotoxicity, but several cancers, including head and neck squamous cell carcinomas (HNSCC), display resistance to TNFα due to activation of the canonical NFκB pro-survival pathway. However, direct targeting of this pathway is associated with significant toxicity; thus, it is vital to identify novel mechanism(s) contributing to NFκB activation and TNFα resistance in cancer cells. Here, we demonstrate that the expression of proteasome-associated deubiquitinase USP14 is significantly increased in HNSCC and correlates with worse progression free survival in Human Papillomavirus (HPV)- HNSCC. Inhibition or depletion of USP14 inhibited the proliferation and survival of HNSCC cells. Further, USP14 inhibition reduced both basal and TNFα-inducible NFκB activity, NFκB-dependent gene expression and the nuclear translocation of the NFκB subunit RELA. Mechanistically, USP14 bound to both RELA and IκBα and reduced IκBα K48-ubiquitination leading to the degradation of IκBα, a critical inhibitor of the canonical NFκB pathway. Furthermore, we demonstrated that b-AP15, an inhibitor of USP14 and UCHL5, sensitized HNSCC cells to TNFα-mediated cell death, as well as radiation-induced cell death in vitro. Finally, b-AP15 delayed tumor growth and enhanced survival, both as a monotherapy and in combination with radiation, in HNSCC tumor xenograft models in vivo, which could be significantly attenuated by TNFα depletion. These data offer new insights into the activation of NFκB signaling in HNSCC and demonstrate that small molecule inhibitors targeting the ubiquitin pathway warrant further investigation as a novel therapeutic avenue to sensitize these cancers to TNFα- and radiation-induced cytotoxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.