ArticleCancer research2009
3-Phosphoinositide-dependent kinase 1 potentiates upstream lesions on the phosphatidylinositol 3-kinase pathway in breast carcinoma.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 137 citations in OpenAlex.
- Focus on 16p13.3 Locus in Colon Cancer.PloS one · 2015Trial
- Influence of DNA copy number and mRNA levels on the expression of breast cancer related proteins.Molecular oncology · 2013Trial
- B4GALNT4-Mediated Glycosylation of PDK1 Activates the PI3K-AKT Signaling Pathway to Promote Prostate Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Acetylcholine enhances HIF-1α signaling in pancreatic cancer cells under hypoxia through the nAChR-α7/PDPK1/YAP pathway.International journal of biological sciences · 2026Article
- Phosphoinositide-dependent kinase 1 (PDK1) in cancer: molecular insights and therapeutic strategies.Frontiers in chemistry · 2026Review
- Recent advances in the role of circRNA in cisplatin resistance in tumors.Cancer gene therapy · 2025Review
- Review
- Review
- Role and targeting of the AGC kinase family in pulmonary fibrosis (Review).Experimental and therapeutic medicine · 2024Review
- Disruption of Autophagic Flux and Treatment with the PDPK1 Inhibitor GSK2334470 Synergistically Inhibit Renal Cell Carcinoma Pathogenesis.Journal of Cancer · 2024Article
- Article
- Anoikis resistance--protagonists of breast cancer cells survive and metastasize after ECM detachment.Cell communication and signaling : CCS · 2023Review
- Advancement of secretory breast carcinoma: a narrative review.Annals of translational medicine · 2022Review
- Pathogenicity Reclassification of Genetic Variants Related to Early-Onset Breast Cancer among Women of Mongoloid Origin.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Activation of the essential kinase PDK1 by phosphoinositide-driven trans-autophosphorylation.Nature communications · 2022Article
- The Landscape of PDK1 in Breast Cancer.Cancers · 2022Review
- SGK1, autophagy and cancer: an overview.Molecular biology reports · 2022Review
- TMEM116 is required for lung cancer cell motility and metastasis through PDK1 signaling pathway.Cell death & disease · 2021Article
- Knockdown of phosphoinositide-dependent kinase 1 (PDK1) inhibits fibrosis and inflammation in lipopolysaccharide-induced acute lung injury rat model by attenuating NF-κB/p65 pathway activation.Annals of translational medicine · 2021Article
- PDK1 Inhibitor BX795 Improves Cisplatin and Radio-Efficacy in Oral Squamous Cell Carcinoma by Downregulating the PDK1/CD47/Akt-Mediated Glycolysis Signaling Pathway.International journal of molecular sciences · 2021Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 12 institutions in 4 countries.
Funding
Abstract
Lesions of ERBB2, PTEN, and PIK3CA activate the phosphatidylinositol 3-kinase (PI3K) pathway during cancer development by increasing levels of phosphatidylinositol-3,4,5-triphosphate (PIP(3)). 3-Phosphoinositide-dependent kinase 1 (PDK1) is the first node of the PI3K signal output and is required for activation of AKT. PIP(3) recruits PDK1 and AKT to the cell membrane through interactions with their pleckstrin homology domains, allowing PDK1 to activate AKT by phosphorylating it at residue threonine-308. We show that total PDK1 protein and mRNA were overexpressed in a majority of human breast cancers and that 21% of tumors had five or more copies of the gene encoding PDK1, PDPK1. We found that increased PDPK1 copy number was associated with upstream pathway lesions (ERBB2 amplification, PTEN loss, or PIK3CA mutation), as well as patient survival. Examination of an independent set of breast cancers and tumor cell lines derived from multiple forms of human cancers also found increased PDK1 protein levels associated with such upstream pathway lesions. In human mammary cells, PDK1 enhanced the ability of upstream lesions to signal to AKT, stimulate cell growth and migration, and rendered cells more resistant to PDK1 and PI3K inhibition. After orthotopic transplantation, PDK1 overexpression was not oncogenic but dramatically enhanced the ability of ERBB2 to form tumors. Our studies argue that PDK1 overexpression and increased PDPK1 copy number are common occurrences in cancer that potentiate the oncogenic effect of upstream lesions on the PI3K pathway. Therefore, we conclude that alteration of PDK1 is a critical component of oncogenic PI3K signaling in breast 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.