ArticleCancer research2022
Lactate Rewires Lipid Metabolism and Sustains a Metabolic-Epigenetic Axis in Prostate Cancer.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 162 citations in OpenAlex.
- Luteolin inhibits prostate cancer stem cells through disrupting the lactate/H3K18la/β-catenin/LDHA feedback loop.Molecular and cellular biochemistry · 2026Article
- Metabolic heterogeneity and functional diversity of cancer-associated fibroblasts in gastric cancer (Review).Oncology letters · 2026Review
- LncRMRP drives bladder cancer invasion via a lactylation-driven positive feedback circuit.Oncogene · 2026Article
- GSTM4 Suppresses Prostate Cancer Progression by Targeting TRIM27-mediated ACLY Ubiquitination and Lipid Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lipid metabolism and chromatin-associated sirtuin-dependent epigenetic reprogramming in cancer.Molecular biology reports · 2026Review
- Cancer-associated adipocytes: metabolic reprogramming, crosstalk and therapeutic implications in tumor progression.Signal transduction and targeted therapy · 2026Review
- Review
- CEBPG-Mediated Palmitic Acid Adaptation of Cancer-Associated Fibroblasts Drives Metastasis of Oral Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Understanding the epigenetic regulation of lactylation and aberrant lactate metabolism in cancer: From mechanisms to therapeutic strategies (Review).International journal of oncology · 2026Review
- CXCR2-mediated metabolic interaction between prostate cancer cells and the immunosuppressive tumor microenvironment.Journal for immunotherapy of cancer · 2026Article
- Lactate-induced H3K4me3 histone mark promotes PLOD1-driven prostate cancer invasion.Cell death & disease · 2026Article
- Decoding the Raf-Mek-Erk-Rsk pathway in prostate cancer: from molecular mechanisms to clinical opportunities.British journal of cancer · 2026Review
- Impact of mitochondrial reductive stress due to respiratory chain limitation on cancer via posttranslational modifications.Redox biology · 2026Review
- Choline metabolism drives metastasis in BRCA1-deficient ovarian cancers by activating FAM3C.Nature communications · 2026Article
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lactic acid promotes metastasis of papillary thyroid carcinoma by enhancing CPT1A lactylation.Cell death & disease · 2026Article
- Lactate and lactylation: metabolic architects of tumor progression and metastasis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- A dual-transformable MgGa-MOF nanoplatform for HCC therapy via lactate metabolism blockade and immune reactivation.Journal of nanobiotechnology · 2026Article
- Probing uric acid-related prognostic genes and their molecular mechanisms in prostate cancer based on transcriptomic data.Discover oncology · 2026Article
- Histone lactylation-driven feedback loop modulates pyrimidine metabolism to promote oral carcinogenesis.Cell death & disease · 2026Article
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
Abstract
Lactate is an abundant oncometabolite in the tumor environment. In prostate cancer, cancer-associated fibroblasts (CAF) are major contributors of secreted lactate, which can be taken up by cancer cells to sustain mitochondrial metabolism. However, how lactate impacts transcriptional regulation in tumors has yet to be fully elucidated. Here, we describe a mechanism by which CAF-secreted lactate is able to increase the expression of genes involved in lipid metabolism in prostate cancer cells. This regulation enhanced intracellular lipid accumulation in lipid droplets (LD) and provided acetyl moieties for histone acetylation, establishing a regulatory loop between metabolites and epigenetic modification. Inhibition of this loop by targeting the bromodomain and extraterminal protein family of histone acetylation readers suppressed the expression of perilipin 2 (PLIN2), a crucial component of LDs, disrupting lactate-dependent lipid metabolic rewiring. Inhibition of this CAF-induced metabolic-epigenetic regulatory loop in vivo reduced growth and metastasis of prostate cancer cells, demonstrating its translational relevance as a therapeutic target in prostate cancer. Clinically, PLIN2 expression was elevated in tumors with a higher Gleason grade and in castration-resistant prostate cancer compared with primary prostate cancer. Overall, these findings show that lactate has both a metabolic and an epigenetic role in promoting prostate cancer progression. SIGNIFICANCE: This work shows that stromal-derived lactate induces accumulation of lipid droplets, stimulates epigenetic rewiring, and fosters metastatic potential in prostate cancer.
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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.