ArticleJournal of experimental & clinical cancer research : CR2023
ACTN1 promotes HNSCC tumorigenesis and cisplatin resistance by enhancing MYH9-dependent degradation of GSK-3β and integrin β1-mediated phosphorylation of FAK.
Article in Journal of experimental & clinical cancer research : CR, 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, 27 citations in OpenAlex.
- BUB1 regulates cell proliferation and apoptosis in cervical cancer by AKT signaling and autophagosome-lysosome fusion via ACTN1.iScience · 2026Article
- Metabolic-epigenetic reprogrammingActa pharmaceutica Sinica. B · 2026Article
- Paeoniflorin inhibits colorectal cancer stem cell properties via regulating LINC01711/KMT2D/KLF7 axis.Journal of gastrointestinal oncology · 2026Article
- HOXC9 enhances cholesterol metabolism and malignancy in pancreatic ductal adenocarcinoma through ITGA10/FAK/PI3K/CREB-dependent HMGCR activation.Journal of gastroenterology · 2026Article
- RBM39 upregulation promotes ostium re-obstruction after endoscopic endonasal dacryocystorhinostomy (En-DCR).BMC molecular and cell biology · 2026Article
- Characterization of aberrant alternative splicing landscape in patients with metastatic renal cell carcinoma.Journal for immunotherapy of cancer · 2026Article
- Unraveling the molecular landscape: an overview on gene expression, epigenetic alterations, and therapeutic challenges in head and neck squamous cell carcinoma.Molecular genetics and genomics : MGG · 2026Review
- OCIAD2 Stabilizes Integrin β1 Signaling Through SNX17-Mediated Endosomal Recycling to Lipid Rafts and Modulates Cisplatin Response in HNSCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- FAM83D facilitates EMT and metastasis of cervical cancer via interaction with GSK3β and inactivation of GSK3β/stabilization of Snail signaling.Biology direct · 2026Article
- The Oncogenic Role of Long Non-Coding RNABiology · 2026Review
- A Genetic Perspective to Reveal the Impact of Mitochondrial Dysfunction-related Genes on Diabetic Kidney Disease: A Multi-omics Study.Current medicinal chemistry · 2026Article
- Integrative single-cell and bulk RNA sequencing unravels the role of ACTN1 in promoting lung cancer with brain metastasis and epidermal growth factor receptor-tyrosine kinase inhibitor resistance.Frontiers in cell and developmental biology · 2026Article
- Multi-omics integration and Mendelian randomization elucidate the PARP16-UPR axis driving chemoresistancein gastric cancer.Frontiers in oncology · 2026Article
- KLHL4 upregulates EGFR signaling to promote the malignant progression of oral squamous cell carcinoma.Medical oncology (Northwood, London, England) · 2025Article
- Lactylation-driven KRT19 promotes non-small cell lung cancer progression by suppressing cellular senescence.Journal of experimental & clinical cancer research : CR · 2025Article
- METTL1-driven epitranscriptomic enhancement of TXNDC12 boosts c-Myc stability through USP5 in HNSCC.Experimental & molecular medicine · 2025Article
- Article
- USP10 stabilizes BAZ1A to drive tumor stemness via an epigenetic mechanism in head and neck squamous cell carcinoma.Cell death & disease · 2025Article
- Integrins in Cancer Drug Resistance: Molecular Mechanisms and Clinical Implications.International journal of molecular sciences · 2025Review
- Integrative single-cell and bulk RNA-seq analysis identifies lactylation-related signature in osteosarcoma.Functional & integrative genomics · 2025Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors globally. Understanding the molecular basis of tumor progression and drug resistance can offer innovative strategies to enhance clinical outcomes for HNSCC patients.
methodsThe cytoskeletal remodeling genes associated with cisplatin resistance were screened using a PCR array. The role of alpha-actinin 1 (ACTN1) in modulating cisplatin resistance and tumorigenesis in HNSCC was evaluated both in vitro and in vivo. Co-immunoprecipitation (Co-IP), IP-mass spectrometry (MS), western blotting, dual-luciferase assay, and bioinformatics analysis were performed to elucidate the underlying mechanisms involved.
resultsOur study identifies ACTN1 as a crucial contributor to cisplatin resistance and tumorigenesis in HNSCC, as evidenced across cellular, animal, and patient-derived xenograft models. From a clinical perspective, overexpression of ACTN1 significantly correlates with a suboptimal response to neoadjuvant chemotherapy and reduced overall survival in HNSCC patients. Mechanistically, ACTN1 predominantly activates β-catenin-mediated signaling by promoting the interaction between myosin heavy chain 9 (MYH9) and GSK-3β, leading to the ubiquitin-dependent degradation of GSK-3β. ACTN1 also interacts with integrin β1, subsequently activating the FAK/PI3K/AKT pathway, providing an additional avenue for the activation of β-catenin signaling. Our study also unveils that the β-catenin/c-Myc axis transcriptionally regulates ACTN1, thereby creating a positive feedback loop promoting HNSCC tumorigenesis and drug resistance.
conclusionsThese insights underscore the novel mechanisms that highlight ACTN1's pivotal role in driving HNSCC progression and resistance to chemotherapy, suggesting ACTN1 as a promising therapeutic target in HNSCC management.
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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.