ArticleSignal transduction and targeted therapy2023
CDK7-YAP-LDHD axis promotes D-lactate elimination and ferroptosis defense to support cancer stem cell-like properties.
Article in Signal transduction and targeted therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 65 citations in OpenAlex.
- Review
- Targeting the KAT7/H3K14ac/RAC2 Axis Mediates OXPHOS to Promote Stemness Maintenance and Malignancy in Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactate-dependent regulation of ferroptosis: redox homeostasis, lactylation, and translational perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
- Unveiling Lactylation: A Novel Frontier in Cancer Stemness and Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lactate and lactylation: metabolic architects of tumor progression and metastasis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- L-Selenomethionine Alleviates Cryo-Induced Ferroptosis Through the NRF2-SLC7A11-GPX4 Pathway, Improving Post-Thaw In Vitro Quality of Dairy Goat Spermatozoa.Antioxidants (Basel, Switzerland) · 2026Article
- The Emerging Role of Transcription-Associated Cyclin-Dependent Kinases in Gastrointestinal Tumors.Cancers · 2026Review
- The Role of Protein Kinases in the Management of Oncological Diseases by Acting on Ferroptotic Pathways.International journal of molecular sciences · 2026Review
- TROP2 confers resistance to oxidative stress-induced cancer cell death through YAP/HMOX1 signaling.Journal of translational medicine · 2026Article
- OTUD4 regulates pancreatic cancer progression via Hippo/YAP axis.Neoplasia (New York, N.Y.) · 2026Article
- Atlas-Guided Nanocarrier Strategies Targeting Spatial NTRK2/MAPK Signaling in EGFR-TKI-Resistant Niches of Esophageal Squamous Cell Carcinoma.Pharmaceutics · 2026Review
- Lactate-lactylation in tumor angiogenesis and progression: mechanisms, biomarker potential, and therapeutic implications.Biomarker research · 2026Review
- The lactate-lactylation axis in tumor radioresistance: metabolic, epigenetic, and immune mechanisms with emerging links to RNA regulation.Frontiers in immunology · 2026Review
- LncRNA FAM66C enhances gastric cancer proliferation and chemoresistance through phosphorylating nuclear YAP protein.Frontiers in pharmacology · 2026Article
- The dual roles of ferroptosis in digestive tract tumors: mechanisms, microenvironment regulation, and therapeutic integration with emphasis on immune interactions.Frontiers in immunology · 2026Review
- Immunosuppressive tumor microenvironment and immunotherapy resistance of esophageal carcinoma.Frontiers in immunology · 2026Review
- YAP as a therapeutic target in esophageal squamous cell carcinoma: insights and strategies.Annals of medicine · 2025Review
- Constructing a sixteen lactate-related gene risk signature for LUAD to predict the prognosis and TME by machine learning.Scientific reports · 2025Article
- Biohybrid nanorobots induce lactate isomer conversion to reverse the immune environment and promote tumor therapy.Science advances · 2025Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reprogrammed cellular metabolism is essential for maintaining cancer stem cells (CSCs) state. Here, we report that mitochondrial D-lactate catabolism is a necessary initiating oncogenic event during tumorigenesis of esophageal squamous cell carcinoma (ESCC). We discover that cyclin-dependent kinase 7 (CDK7) phosphorylates nuclear Yes-associated protein 1 (YAP) at S127 and S397 sites and enhances its transcription function, which promotes D-lactate dehydrogenase (LDHD) protein expression. Moreover, LDHD is enriched significantly in ESCC-CSCs rather than differentiated tumor cells and high LDHD status is connected with poor prognosis in ESCC patients. Mechanistically, the CDK7-YAP-LDHD axis helps ESCC-CSCs escape from ferroptosis induced by D-lactate and generates pyruvate to satisfy energetic demands for their elevated self-renewal potential. Hence, we conclude that esophageal CSCs adopt a D-lactate elimination and pyruvate accumulation mode dependent on CDK7-YAP-LDHD axis, which drives stemness-associated hallmarks of ESCC-CSCs. Reasonably, targeting metabolic checkpoints may serve as an effective strategy for ESCC therapy.
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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.