ArticleThe Journal of clinical investigation2018
Mitochondrial reprogramming via ATP5H loss promotes multimodal cancer therapy resistance.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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.
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Who cites it
33 citing papers in PubMed, 44 citations in OpenAlex.
- Tumor Cells as Architects of Immune Refractoriness: Dismantling Intrinsic Programs of Tumor Cells for Clinical Translation.Immune network · 2026Review
- PARylation-centric crosstalk: orchestrating immune evasion and multidrug resistance in ovarian cancer.Frontiers in immunology · 2026Review
- Biobanking of gynecologic cancer biospecimens: Development, quality control, and translational applications.PloS one · 2026Article
- The E2F1-HMGCR axis promotes ferroptosis resistance in immune refractory tumor cells.Nature communications · 2025Article
- Neutrophil extracellular traps in tumor metabolism and microenvironment.Biomarker research · 2025Review
- The role of complement in tumor immune tolerance and drug resistance: a double-edged sword.Frontiers in immunology · 2025Review
- The selenoenzyme type I iodothyronine deiodinase: a new tumor suppressor in ovarian cancer.Molecular oncology · 2024Article
- Comparative Proteomic Identification of Ram Sperm before and after In Vitro Capacitation.Animals : an open access journal from MDPI · 2024Article
- Developing a comprehensive molecular subgrouping model for cervical cancer using machine learning.American journal of cancer research · 2024Article
- Dihydroartemisinin inhibits liver cancer cell migration and invasion by reducing ATP synthase production through CaMKK2/NCLX.Oncology letters · 2023Article
- Ferroptosis and tumor immunotherapy: A promising combination therapy for tumors.Frontiers in oncology · 2023Review
- Gene crosstalk between COVID-19 and preeclampsia revealed by blood transcriptome analysis.Frontiers in immunology · 2023Article
- Genome ofInternational journal of molecular sciences · 2022Article
- Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management.Journal of hematology & oncology · 2022Review
- NANOG confers resistance to complement-dependent cytotoxicity in immune-edited tumor cells through up-regulating CD59.Scientific reports · 2022Article
- Mapping the Cord Blood Transcriptome of Pregnancies Affected by Early Maternal Anemia to Identify Signatures of Fetal Programming.The Journal of clinical endocrinology and metabolism · 2022Article
- Targeting the NANOG/HDAC1 axis reverses resistance to PD-1 blockade by reinvigorating the antitumor immunity cycle.The Journal of clinical investigation · 2022Article
- New spinocerebellar ataxia subtype caused byBrain communications · 2022Article
- Redox signaling and metabolism in Alzheimer's disease.Frontiers in aging neuroscience · 2022Review
- The promise of targeting heme and mitochondrial respiration in normalizing tumor microenvironment and potentiating immunotherapy.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
21 authors at 11 institutions in 5 countries.
Funding
Abstract
The host immune system plays a pivotal role in the emergence of tumor cells that are refractory to multiple clinical interventions including immunotherapy, chemotherapy, and radiotherapy. Here, we examined the molecular mechanisms by which the immune system triggers cross-resistance to these interventions. By examining the biological changes in murine and tumor cells subjected to sequential rounds of in vitro or in vivo immune selection via cognate cytotoxic T lymphocytes, we found that multimodality resistance arises through a core metabolic reprogramming pathway instigated by epigenetic loss of the ATP synthase subunit ATP5H, which leads to ROS accumulation and HIF-1α stabilization under normoxia. Furthermore, this pathway confers to tumor cells a stem-like and invasive phenotype. In vivo delivery of antioxidants reverses these phenotypic changes and resensitizes tumor cells to therapy. ATP5H loss in the tumor is strongly linked to failure of therapy, disease progression, and poor survival in patients with cancer. Collectively, our results reveal a mechanism underlying immune-driven multimodality resistance to cancer therapy and demonstrate that rational targeting of mitochondrial metabolic reprogramming in tumor cells may overcome this resistance. We believe these results hold important implications for the clinical management of cancer.
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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.