ArticleCell death & disease2023
MELK promotes HCC carcinogenesis through modulating cuproptosis-related gene DLAT-mediated mitochondrial function.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 71 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
71 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.
- The molecular mechanism of cuproptosis and research progress in pancreatic diseases.Annals of medicine · 2026Pooled it
- Coping with copper: a bibliometric analysis of copper's role in cancer pathogenesis and treatment.Systematic reviews · 2025Pooled it
- The role of copper and cuproptosis in digestive system cancers: novel therapeutic strategies and mechanistic insights.Cancer biology & therapy · 2026Review
- Harnessing copper-iron crosstalk: A novel strategy to combat hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Review
- UBE2D4 Upregulation Promotes Cuproptosis Sensitivity in Colorectal Cancer.Molecular genetics & genomic medicine · 2026Article
- Review
- Harnessing Cuproptosis for Antitumor Immunity: A Review of Current Evidence and Therapeutic Strategies.Molecular carcinogenesis · 2026Review
- MELK inhibits cuproptosis in diffuse large B-cell lymphoma cells via the PI3K/mTOR/S6K-DLAT signaling axis.Molecular and cellular biochemistry · 2026Article
- Mitochondrial dynamics imbalance in hepatocellular carcinoma: from molecular mechanisms to new strategies for targeted therapy.Translational cancer research · 2026Review
- Article
- Cuproptosis: potential new direction in liver-related diseases research and treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- GSH-Responsive Nanoparticles Enhance Hepatocellular Carcinoma Immunotherapy Through Synergistic Effects of Cuproptosis and PI3K Inhibitor Combination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cuproptosis causes meiotic metaphase I arrest by disrupting mitochondrial functions in oocytes.Cell death discovery · 2026Article
- Development and validation of a cuproptosis-related gene signature for predicting prognosis and drug sensitivity in gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- RCDRank: a web server to prioritize regulated cell death modalities.BMC bioinformatics · 2026Article
- PRR15 suppresses renal cell carcinoma progression via the NF-κB/FDX1 axis to induce cuproptosis and mitochondrial dysfunction.Oncogene · 2026Article
- Role of cuproptosis in digestive system tumors (Review).International journal of molecular medicine · 2026Review
- Maternal Embryonic Leucine Zipper Kinase (Biology · 2026Review
- Harnessing Cuproptosis resistance to advance cancer therapeutics.Apoptosis : an international journal on programmed cell death · 2026Review
- Ferroptosis and cuproptosis in head and neck squamous cell carcinoma: interconnected mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cuproptosis caused by copper overload is mediated by a novel regulatory mechanism that differs from previously documented mechanisms regulating cell death. Cells dependent on mitochondrial respiration showed increased sensitivity to a copper ionophore elesclomol that induced cuproptosis. Maternal embryonic leucine zipper kinase(MELK) promotes tumorigenesis and tumor progression through the PI3K/mTOR pathway, which exerts its effects partly by targeting the pyruvate dehydrogenase complex(PDHc) and reprogramming the morphology and function of mitochondria. However, the role of MELK in cuproptosis remains unclear. Here, we validated that elevated MELK expression enhanced the activity of PI3K/mTOR signaling and subsequently promoted Dihydrolipoamide S-Acetyltransferase (DLAT) expression and stabilized mitochondrial function. This regulatory effect helped to improve mitochondrial respiration, eliminate excessive intracellular reactive oxygen species (ROS), reduce intracellular oxidative stress/damage and the possibility of mitochondria-induced cell fate alternations, and ultimately promote the progression of HCC. Meanwhile, elesclomol reduced translocase of outer mitochondrial membrane 20(TOM 20) expression and increased DLAT oligomers. Moreover, the above changes of MELK to HCC were abolished by elesclomol. In conclusion, MELK enhanced the levels of the cuproptosis-related signature(CRS) gene DLAT (especially the proportion of DLAT monomer) by activating the PI3K/mTOR pathway, thereby promoting elesclomol drug resistance, altering mitochondrial function, and ultimately promoting HCC progression.
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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.