ArticleCell death & disease2022
Lon upregulation contributes to cisplatin resistance by triggering NCLX-mediated mitochondrial Ca
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Cancer-associated mitochondrial homeostasis disrupted and retrograde signaling activated.Medical oncology (Northwood, London, England) · 2026Review
- Cell-intrinsic and tumor microenvironmental determinants of platinum resistance in epithelial ovarian cancer.Discover oncology · 2026Review
- Autophagy initiation inhibition combined with chemotherapy reverses drug resistance in oral cancer.Discover oncology · 2026Review
- The importance of mitochondria and mitochondrial calcium signaling in health and disease: an updated outlook on inflammation.Journal of translational medicine · 2026Review
- Mitochondria-associated membranes in heart failure: from molecular mechanisms to therapeutic targets.Frontiers in physiology · 2026Review
- Article
- LONP1 regulation of mitochondrial protein folding provides insight into beta cell failure in type 2 diabetes.Nature metabolism · 2025Article
- Unraveling Cathepsin S regulation in interleukin-7-mediated anti-tumor immunity reveals its targeting potential against oral cancer.Journal of biomedical science · 2025Article
- Review
- Crosstalk between calcium and reactive oxygen species signaling in cancer revisited.Cell calcium · 2025Review
- Calcium channels as pharmacological targets for cancer therapy.Clinical and experimental medicine · 2025Review
- Research progress of PYK2 in digestive system diseases.Frontiers in immunology · 2025Review
- The mitochondrial stress signaling tunes immunity from a view of systemic tumor microenvironment and ecosystem.iScience · 2024Review
- Research progress on mitochondria regulating tumor immunity.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- Article
- Dihydroartemisinin inhibits liver cancer cell migration and invasion by reducing ATP synthase production through CaMKK2/NCLX.Oncology letters · 2023Article
- Tumor Cells Transmit Drug Resistance via Cisplatin-Induced Extracellular Vesicles.International journal of molecular sciences · 2023Review
- Role of mitochondrial alterations in human cancer progression and cancer immunity.Journal of biomedical science · 2023Review
- Genomic Landscape and Potential Regulation of RNA Editing in Drug Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Mitochondrial Lon-induced mitophagy benefits hypoxic resistance via CaCell death & disease · 2023Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondria are the major organelles in sensing cellular stress and inducing the response for cell survival. Mitochondrial Lon has been identified as an important stress protein involved in regulating proliferation, metastasis, and apoptosis in cancer cells. However, the mechanism of retrograde signaling by Lon on mitochondrial DNA (mtDNA) damage remains to be elucidated. Here we report the role of Lon in the response to cisplatin-induced mtDNA damage and oxidative stress, which confers cancer cells on cisplatin resistance via modulating calcium levels in mitochondria and cytosol. First, we found that cisplatin treatment on oral cancer cells caused oxidative damage of mtDNA and induced Lon expression. Lon overexpression in cancer cells decreased while Lon knockdown sensitized the cytotoxicity towards cisplatin treatment. We further identified that cisplatin-induced Lon activates the PYK2-SRC-STAT3 pathway to stimulate Bcl-2 and IL-6 expression, leading to the cytotoxicity resistance to cisplatin. Intriguingly, we found that activation of this pathway is through an increase of intracellular calcium (Ca
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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.