ArticleApoptosis : an international journal on programmed cell death2024
EVA1A reverses lenvatinib resistance in hepatocellular carcinoma through regulating PI3K/AKT/p53 signaling axis.
Article in Apoptosis : an international journal on programmed cell death, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- p53-R280S mutation confers lenvatinib resistance in hepatocellular carcinoma via Bcl-2-mediated anti-apoptotic signaling.Molecular and cellular biochemistry · 2026Article
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- EVA1A-Mediated Signaling Networks in Physiological and Pathological Contexts: Dual Roles in Autophagy and Apoptosis.Cell biochemistry and biophysics · 2026Review
- [EVA1A overexpression improves non-alcoholic fatty liver disease in mice by regulating lipid metabolism and promoting lipophagy].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- The tryptanthrin derivative g2 suppresses tongue squamous cell carcinoma via PI3K/AKT/P53 cathway modulation: evidence fromFrontiers in pharmacology · 2026Article
- The role and mechanism of CHST6-mediated lactation modification in lenvatinib resistance in hepatocellular carcinoma cells.American journal of translational research · 2026Article
- The Quartet of Core Oncogenic Drivers in Neuroendocrine Prostate Cancer: Multi-Omics Dataset Integration to Forge a Translational Link Between Biology and Precision Therapy.International journal of biological sciences · 2026Review
- Targeting the MIR4435-2HG/miR-29c-3p/FSP1 axis overcomes lenvatinib resistance by inducing ferroptosis in hepatocellular carcinoma.Cancer cell international · 2025Article
- AFP promotes cancer multidrug resistance through activating PI3K/Akt/NF-κB signaling pathway.Scientific reports · 2025Article
- TMEM166 negatively regulates unfolded protein response to affect hepatocellular carcinoma cell growth and sorafenib resistance.Cell death & disease · 2025Article
- Mechanisms of drug resistance in hepatocellular carcinoma.Biological procedures online · 2025Review
- The Role and Mechanism of Innate Immune Regulation in Overcoming Oxaliplatin Resistance and Enhancing Anti-Tumor Efficacy in Colorectal Cancer.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Regulated Cell Death in Lenvatinib Resistance of Hepatocellular Carcinoma: from Molecular Mechanisms to Therapeutic Strategies.International journal of biological sciences · 2025Review
- EVA1A Regulates Hepatic Lipid Homeostasis by Modulating CD36 Expression and Its Palmitoylation.Research (Washington, D.C.) · 2025Article
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Authors and funding
12 authors.
Funding
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Abstract
Lenvatinib is a commonly used first-line drug for the treatment of advanced hepatocellular carcinoma (HCC). However, its clinical efficacy is limited due to the drug resistance. EVA1A was a newly identified tumor suppressor, nevertheless, the impact of EVA1A on resistance to lenvatinib treatment in HCC and the potential molecular mechanisms remain unknown. In this study, the expression of EVA1A in HCC lenvatinib-resistant cells is decreased and its low expression was associated with a poor prognosis of HCC. Overexpression of EVA1A reversed lenvatinib resistance in vitro and in vivo, as demonstrated by its ability to promote cell apoptosis and inhibit cell proliferation, invasion, migration, EMT, and tumor growth. Silencing EVA1A in lenvatinib-sensitive parental HCC cells exerted the opposite effect and induced resistance to lenvatinib. Mechanistically, upregulated EVA1A inhibited the PI3K/AKT/MDM2 signaling pathway, resulting in a reduced interaction between MDM2 and p53, thereby stabilizing p53 and enhancing its antitumor activity. In addition, upregulated EVA1A suppressed the PI3K/AKT/mTOR signaling pathway and promoted autophagy, leading to the degradation of mutant p53 and attenuating its oncogenic impact. On the contrary, loss of EVA1A activated the PI3K/AKT/MDM2 signaling pathway and inhibited autophagy, promoting p53 proteasomal degradation and mutant p53 accumulation respectively. These findings establish a crucial role of EVA1A loss in driving lenvatinib resistance involving a mechanism of modulating PI3K/AKT/p53 signaling axis and suggest that upregulating EVA1A is a promising therapeutic strategy for alleviating resistance to lenvatinib, thereby improving the efficacy of HCC treatment.
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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 Socratic graph.