ArticleOncotarget2016
Activation of AKT pathway by Nrf2/PDGFA feedback loop contributes to HCC progression.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Platelet-to-lymphocyte ratio in the setting of liver transplantation for hepatocellular cancer: A systematic review and meta-analysis.World journal of gastroenterology · 2018Pooled it
- Distinct Interactions of Arsenite and Cadmium with Metal Homeostasis and the Cellular Stress Response in Human Bronchial Epithelial Cells.International journal of molecular sciences · 2026Article
- The PI3K pathway is a downstream effector of NRF2 activation in the esophagus.Translational oncology · 2026Article
- Elevated SNHG1 promotes invasion and migration of Cd(II)-transformed cells through Sox2, Rac1, and Slug.Toxicology and applied pharmacology · 2025Article
- Transcriptome and Proteome Analyses Revealed Differences in JEV-Infected PK-15 Cells in Response to Ferroptosis Agonists and Antagonists.Animals : an open access journal from MDPI · 2024Article
- Advances in Nrf2 Signaling Pathway by Targeted Nanostructured-Based Drug Delivery Systems.Biomedicines · 2024Review
- The NRF-2/HO-1 Signaling Pathway: A Promising Therapeutic Target for Metabolic Dysfunction-Associated Steatotic Liver Disease.Journal of inflammation research · 2024Review
- Nrf2 Transcriptional Activity Governs Intestine Development.International journal of molecular sciences · 2022Article
- Brucein D augments the chemosensitivity of gemcitabine in pancreatic cancer via inhibiting the Nrf2 pathway.Journal of experimental & clinical cancer research : CR · 2022Article
- The role of polyphenols in overcoming cancer drug resistance: a comprehensive review.Cellular & molecular biology letters · 2022Review
- Smart FeInternational journal of nanomedicine · 2022Article
- Development of targeted therapy of NRF2Cellular signalling · 2021Review
- CCL23 suppresses liver cancer progression through the CCR1/AKT/ESR1 feedback loop.Cancer science · 2021Article
- Antioxidative Stress: Inhibiting Reactive Oxygen Species Production as a Cause of Radioresistance and Chemoresistance.Oxidative medicine and cellular longevity · 2021Review
- NRF2 preserves genomic integrity by facilitating ATR activation and G2 cell cycle arrest.Nucleic acids research · 2020Article
- Molecular Mechanisms Underlying Hepatocellular Carcinoma Induction by Aberrant NRF2 Activation-Mediated Transcription Networks: Interaction of NRF2-KEAP1 Controls the Fate of Hepatocarcinogenesis.International journal of molecular sciences · 2020Review
- NRF2 as a regulator of cell metabolism and inflammation in cancer.Carcinogenesis · 2020Review
- NRF2 activates growth factor genes and downstream AKT signaling to induce mouse and human hepatomegaly.Journal of hepatology · 2020Article
- Astaxanthin Treatment Induces Maturation and Functional Change of Myeloid-Derived Suppressor Cells in Tumor-Bearing Mice.Antioxidants (Basel, Switzerland) · 2020Article
- Overexpression of Nrf2 promotes colon cancer progression via ERK and AKT signaling pathways.Annals of surgical treatment and research · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear factor erythroid-2-related factor 2 (Nrf2), a master transcription factor in the antioxidant response, has been found to be ubiquitously expressed in various cancer cells and in the regulation tumor proliferation, invasion, and chemoresistance activities. The regulatory roles of Nrf2 in controlling Hepatocellular carcinoma (HCC) progression remain unclear. In this study, we demonstrated that Nrf2 was significantly elevated in HCC cells and tissues and was correlated with poor prognosis of HCCs. Consistently, Nrf2 significantly promoted HCC cell growth both in vitro and in vivo. Further investigation suggested a novel association of Nrf2 with Platelet-Derived Growth Factor-A (PDGFA). Nrf2 promoted PDGFA transcription by recruiting specificity protein 1 (Sp1) to its promoter, resulting in increased activation of the AKT/p21 pathway and cell cycle progression of HCC cells. As a feedback loop, PDGFA enhanced Nrf2 expression and activation in an AKT dependent manner. In line with these findings, expression of Nrf2 and PDGFA were positively correlated in HCC tissues. Taken together, this study uncovers a novel mechanism of the Nrf2/PDGFA regulatory loop that is crucial for AKT-dependent HCC progression, and thereby provides potential targets for HCC therapy.
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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.