ArticleOncotarget2015
The Akt1/IL-6/STAT3 pathway regulates growth of lung tumor initiating cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
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- UHPLC -Q-Orbitrap HRMS Integrated with Network Pharmacology Reveals the Anti-COPD Mechanism of Jianzhong Peiyuan Decoction and Functional Validation of Core Component Luteolin.Journal of inflammation research · 2026Article
- Meprin β activity modulates cellular proliferation via trans-signaling IL-6-mediated AKT/ERK pathway in IR-induced kidney injury.BMC nephrology · 2025Article
- The Role of Fat Mass and Obesity-Associated (FTO) Gene in Non-Small Cell Lung Cancer Tumorigenicity and EGFR Tyrosine Kinase Inhibitor Resistance.Biomedicines · 2025Article
- Combination of RNA-sequencing data analysis, network pharmacology, molecular docking techniques to investigate the mechanism of Prunella vulgaris L. in the treatment of non-small cell lung cancer.Discover oncology · 2025Article
- Identification of the role of sugar-sweetened beverages in the progression of a murine metabolic dysfunction-associated steatotic liver disease model.Frontiers in nutrition · 2025Article
- Leucine-973 is a crucial residue differentiating insulin and IGF-1 receptor signaling.The Journal of clinical investigation · 2023Article
- Exploration and validation of hub genes in lung adenocarcinoma based on bioinformatics analysis.Translational cancer research · 2022Article
- LRP5 promotes cancer stem cell traits and chemoresistance in colorectal cancer.Journal of cellular and molecular medicine · 2022Article
- Knockdown lncRNA NEAT1 regulates the activation of microglia and reduces AKT signaling and neuronal apoptosis after cerebral ischemic reperfusion.Scientific reports · 2020Article
- HSulf‑1 and palbociclib exert synergistic antitumor effects on RB‑positive triple‑negative breast cancer.International journal of oncology · 2020Article
- Article
- Distinct functions of AKT isoforms in breast cancer: a comprehensive review.Cell communication and signaling : CCS · 2019Review
- PTEN Tumor-Suppressor: The Dam of Stemness in Cancer.Cancers · 2019Review
- Hepatocyte Nuclear Factor 3β Plays a Suppressive Role in Colorectal Cancer Progression.Frontiers in oncology · 2019Article
- Targeting CXCL12/CXCR4 Axis in Tumor Immunotherapy.Current medicinal chemistry · 2019Review
- Transcriptional profiling of human bronchial epithelial cell BEAS-2B exposed to diesel and biomass ultrafine particles.BMC genomics · 2018Article
- Preclinical Evidence for Combined Use of Aromatase Inhibitors and NSAIDs as Preventive Agents of Tobacco-Induced Lung Cancer.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2018Article
- HSP70L1-mediated intracellular priming of dendritic cell vaccination induces more potent CTL response against cancer.Cellular & molecular immunology · 2018Article
- Cadherin-26 (CDH26) regulates airway epithelial cell cytoskeletal structure and polarity.Cell discovery · 2018Article
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Here we report that the PI3K/Akt1/IL-6/STAT3 signalling pathway regulates generation and stem cell-like properties of Non-Small Cell Lung Cancer (NSCLC) tumor initiating cells (TICs). Mutant Akt1, mutant PIK3CA or PTEN loss enhances formation of lung cancer spheroids (LCS), self-renewal, expression of stemness markers and tumorigenic potential of human immortalized bronchial cells (BEAS-2B) whereas Akt inhibition suppresses these activities in established (NCI-H460) and primary NSCLC cells. Matched microarray analysis of Akt1-interfered cells and LCSs identified IL-6 as a critical target of Akt signalling in NSCLC TICs. Accordingly, suppression of Akt in NSCLC cells decreases IL-6 levels, phosphorylation of IkK and IkB, NF-kB transcriptional activity, phosphorylation and transcriptional activity of STAT3 whereas active Akt1 up-regulates them. Exposure of LCSs isolated from NSCLC cells to blocking anti-IL-6 mAbs, shRNA to IL-6 receptor or to STAT3 markedly reduces the capability to generate LCSs, to self-renew and to form tumors, whereas administration of IL-6 to Akt-interfered cells restores the capability to generate LCSs. Finally, immunohistochemical studies in NSCLC patients demonstrated a positive correlative trend between activated Akt, IL-6 expression and STAT3 phosphorylation (n = 94; p < 0.05). In conclusion, our data indicate that aberrant Akt signalling contributes to maintaining stemness in lung cancer TICs through a NF-kB/IL-6/STAT3 pathway and provide novel potential therapeutic targets for eliminating these malignant cells in NSCLC.
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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.