ArticlePLoS biology2024
KCNK1 promotes proliferation and metastasis of breast cancer cells by activating lactate dehydrogenase A (LDHA) and up-regulating H3K18 lactylation.
Article in PLoS biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed.
- OLR1 promotes cell proliferation and invasion while represses apoptosis via regulating histone H3 lysine 18 lactylation‑mediated LEMD1 in papillary thyroid cancer.Oncology reports · 2026Article
- Unveiling isoleucyl-tRNA synthetase 2 as a novel driver of breast cancer via β-catenin pathway activation.Journal of cell communication and signaling · 2026Article
- H3K18 Lactylation Promotes Cell Proliferation in T-Cell Acute Lymphoblastic Leukemia.Journal of cellular biochemistry · 2026Article
- Potassium channels in cancer: from hallmarks to therapeutic targeting.Journal of physiology and biochemistry · 2026Review
- Research progress of lactylation modification in tumors (Review).Experimental and therapeutic medicine · 2026Review
- Expression of LDHA, Pan-Kla Level and H3K18la associates with clinical progression of laryngeal squamous cell carcinoma.Diagnostic pathology · 2026Article
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Lactate-driven metabolic-epigenetic reprogramming in breast cancer: immune evasion and therapeutic resistance.Clinical epigenetics · 2026Review
- Lactylation in cancer: a new frontier in metabolic-epigenetic regulation and clinical practice.Cell communication and signaling : CCS · 2026Review
- Protein lactylation in cancer: principles, programmes and therapeutic opportunities.Molecular cancer · 2026Review
- Lactylation-driven therapeutic resistance in cancer: Mechanisms and therapeutic opportunities.Genes & diseases · 2026Review
- Impact of mitochondrial reductive stress due to respiratory chain limitation on cancer via posttranslational modifications.Redox biology · 2026Review
- Lactate in ruminant health: metabolic roles and the emerging significance of lactylation.Journal of animal science and biotechnology · 2026Review
- DDX39B drives the m6A modification of LDHA to promote trophoblast proliferation.Molecular genetics and genomics : MGG · 2026Article
- Metabolic activation of LDHA by ERRα represses inflammasome-dependent pyroptosis and promotes ovarian cancer chemoresistance.Cell death & disease · 2026Article
- Data Resources and Computational Methods for Lactylation Site Prediction: A Mini-Review.International journal of molecular sciences · 2026Review
- Construction of a Lysine Lactylation- and DNA Damage Repair-Related Gene Signature to Predict the Prognosis and Drug Sensitivity of Breast Cancer Patients.International journal of molecular sciences · 2026Article
- LDHC4 drives lung adenocarcinoma progression by inducing lactylation of RB1 at lysine 900 to disrupt the RB1-E2F1 complex.Journal of translational medicine · 2026Article
- Role and clinical importance of lactylation in tumors (Review).Molecular medicine reports · 2026Review
- LDHA-driven ACAA2 lactylation at K270 reprograms fatty acid metabolism to promote clear cell renal cell carcinoma progression.Scientific reports · 2026Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors.
Funding
Abstract
Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily K Member 1 (KCNK1) is differentially expressed in a variety of tumors, but the mechanism of its function in breast cancer is unknown. In this study, we found for the first time that KCNK1 was significantly up-regulated in human breast cancer and was correlated with poor prognosis in breast cancer patients. KCNK1 promoted breast cancer proliferation, invasion, and metastasis in vitro and vivo. Further studies unexpectedly revealed that KCNK1 increased the glycolysis and lactate production in breast cancer cells by binding to and activating lactate dehydrogenase A (LDHA), which promoted histones lysine lactylation to induce the expression of a series of downstream genes and LDHA itself. Notably, increased expression of LDHA served as a vicious positive feedback to reduce tumor cell stiffness and adhesion, which eventually resulted in the proliferation, invasion, and metastasis of breast cancer. In conclusion, our results suggest that KCNK1 may serve as a potential breast cancer biomarker, and deeper insight into the cancer-promoting mechanism of KCNK1 may uncover a novel therapeutic target for breast cancer treatment.
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