ArticleOncogenesis2020
PDK1 promotes ovarian cancer metastasis by modulating tumor-mesothelial adhesion, invasion, and angiogenesis via α5β1 integrin and JNK/IL-8 signaling.
Article in Oncogenesis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 73 citations in OpenAlex.
- Metabolic reprogramming and cisplatin resistance: the emerging role of Pyruvate Dehydrogenase Kinases (PDKs).Cell communication and signaling : CCS · 2026Review
- Targeting Phosphoinositide 3-Kinase to Reduce the Progression of Ovarian Cancer Cells in a 3D Collagen Model.Biomolecules · 2026Article
- Glycolytic reprogramming in ovarian cancer: mechanisms, immune crosstalk, and therapeutic implications.Frontiers in immunology · 2026Review
- Phosphoinositide-dependent kinase 1 (PDK1) in cancer: molecular insights and therapeutic strategies.Frontiers in chemistry · 2026Review
- Apoptosis of Mesothelial Cells Is Associated with the Pattern of Peritoneal Metastases in Ovarian Cancer.Cancers · 2025Article
- Identifying regulators of aged fibroblast activation in 3D tissue models.Scientific reports · 2025Article
- SOAT1 in ovarian cancer cells regulates immune response mediated by CD8Journal of ovarian research · 2025Article
- Metabolic Reprogramming of Cancer Cells and Therapeutics Targeting Cancer Metabolism.Cancer medicine · 2025Review
- Role of tumor microenvironment in ovarian cancer metastasis and clinical advancements.Journal of translational medicine · 2025Review
- Navigating Metabolic Challenges in Ovarian Cancer: Insights and Innovations in Drug Repurposing.Cancer medicine · 2025Review
- PDK1, associated with glycolytic metabolism, is a potential prognostic biomarker in osteosarcoma.PloS one · 2025Article
- PIWIL2/PDK1 Axis Promotes the Progression of Cervical Epithelial Lesions via Metabolic Reprogramming to Maintain Tumor-Initiating Cell Stemness.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- PDK1 promotes epithelial ovarian cancer progression by upregulating BGN.Acta biochimica et biophysica Sinica · 2024Article
- Targeting interleukin-6 as a treatment approach for peritoneal carcinomatosis.Journal of translational medicine · 2024Review
- Article
- A Recipe for Successful Metastasis: Transition and Migratory Modes of Ovarian Cancer Cells.Cancers · 2024Review
- Exploring osteosarcoma based on the tumor microenvironment.Frontiers in immunology · 2024Article
- Glucose metabolism reprogramming in gynecologic malignant tumors.Journal of Cancer · 2024Review
- Gastric cancer mesenchymal stem cells via the CXCR2/HK2/PD-L1 pathway mediate immunosuppression.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2023Article
- Cancer-mesothelial and cancer-macrophage interactions in the ovarian cancer microenvironment.American journal of physiology. Cell physiology · 2023Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ovarian cancer is the most lethal gynecological malignancies owing to the lack of definitive symptoms until development of widespread metastases. Identification of novel prognostic and therapeutic targets is therefore an urgent need to improve survival. Here, we demonstrated high expression of the mitochondrial gatekeeping enzyme, pyruvate dehydrogenase kinase 1 (PDK1), in both clinical samples and cell lines of ovarian cancer. PDK1 expression was significantly associated with metastasis, reduced chemosensitivity, and poor overall and disease-free survival, and further highlighted as an independent prognostic factor. Silencing of PDK1 retarded lactate production, ovarian cancer cell adhesion, migration, invasion, and angiogenesis, and consequently metastasis, concomitant with decreased α5β1 integrin expression. Phospho-kinase array profiling and RNA sequencing analyses further revealed reduction of JNK activation and IL-8 expression in PDK1-depleted cells. Conversely, PDK1 overexpression promoted cell adhesion via modulation of α5β1 integrins, along with cell migration, invasion, and angiogenesis through activation of JNK/IL-8 signaling. PDK1 depletion additionally hindered tumor growth and dissemination in nude mice in vivo. Importantly, PDK1 levels were upregulated upon treatment with conditioned medium from omental tissues, which in turn promoted metastasis. Our findings suggest that PDK1, which is regulated by the tumor microenvironment, controls lactate production and promotes ovarian cancer cell metastasis via modulation of α5β1 integrin and JNK/IL-8 signaling. To our knowledge, this is the first report to demonstrate an association between PDK1 and survival in patients with ovarian cancer, supporting its efficacy as a valuable prognostic marker and therapeutic molecular target for the disease.
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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.