ArticleOncogene2014
PDK1 controls upstream PI3K expression and PIP3 generation.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
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- Transcriptomics, identification, and testing of manganese metabolism-related genes in cervical squamous cell carcinoma.Frontiers in oncology · 2026Article
- Identifying C1orf122 as a potential HCC exacerbated biomarker dependently of SRPK1 regulates PI3K/AKT/GSK3β signaling pathway.Genes & diseases · 2026Article
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- Ovarian Mechanobiology: Understanding the Interplay Between Mechanics and Follicular Development.Cells · 2025Review
- Pharmacological Perspective on the Neurobiology of PI3K-Akt-mTOR Signalling in Opioid Dependence.CNS & neurological disorders drug targets · 2025Review
- Hespintor Negative Regulation of PI3K/Akt Pathway Induces Cell Cycle Arrest of Hepatocellular Carcinoma.Bulletin of experimental biology and medicine · 2024Article
- SPINK13 acts as a tumor suppressor in hepatocellular carcinoma by inhibiting Akt phosphorylation.Cell death & disease · 2024Article
- Lipids associated with autophagy: mechanisms and therapeutic targets.Cell death discovery · 2024Review
- The DLEU2/miR-15a/miR-16-1 cluster shapes the immune microenvironment of chronic lymphocytic leukemia.Blood cancer journal · 2024Article
- Targeting PI3K/Akt in Cerebral Ischemia Reperfusion Injury Alleviation: From Signaling Networks to Targeted Therapy.Molecular neurobiology · 2024Review
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- Roles of phosphatidylinositol-3-kinases signaling pathway in inflammation-related cancer: Impact of rs10889677 variant and buparlisib in colitis-associated cancer.World journal of gastroenterology · 2023Article
- Article
- Circular RNAs Involved in the Regulation of the Age-Related Pathways.International journal of molecular sciences · 2022Review
- Oncogenic potential of BEST4 in colorectal cancer via activation of PI3K/Akt signaling.Oncogene · 2022Article
- Crosstalk between circRNAs and the PI3K/AKT signaling pathway in cancer progression.Signal transduction and targeted therapy · 2021Review
- Targeting the PI3K/Akt/mTOR Pathway in Hepatocellular Carcinoma.Biomedicines · 2021Review
- Proteomic analysis of a murine model of lung hypoplasia induced by oligohydramnios.Pediatric pulmonology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
The PI3K/PDK1/Akt signaling axis is centrally involved in cellular homeostasis and controls cell growth and proliferation. Due to its key function as regulator of cell survival and metabolism, the dysregulation of this pathway is manifested in several human pathologies including cancers and immunological diseases. Thus, current therapeutic strategies target the components of this signaling cascade. In recent years, numerous feedback loops have been identified that attenuate PI3K/PDK1/Akt-dependent signaling. Here, we report the identification of an additional level of feedback regulation that depends on the negative transcriptional control of phosphatidylinositol 3-kinase (PI3K) class IA subunits. Genetic deletion of 3-phosphoinositide-dependent protein kinase 1 (PDK1) or the pharmacological inhibition of its downstream effectors, that is, Akt and mammalian target of rapamycin (mTOR), relieves this suppression and leads to the upregulation of PI3K subunits, resulting in enhanced generation of phosphatidylinositol-3,4,5-trisphosphate (PIP3). Apparently, this transcriptional induction is mediated by the concerted action of different transcription factor families, including the transcription factors cAMP-responsive element-binding protein and forkhead box O. Collectively, we propose that PDK1 functions as a cellular sensor that balances basal PIP3 generation at levels sufficient for survival but below a threshold being harmful to the cell. Our study suggests that the efficiency of therapies targeting the aberrantly activated PI3K/PDK1/Akt pathway might be increased by the parallel blockade of feedback circuits.
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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.