ArticleCancer science2011
Roles of AKT1 and AKT2 in non-small cell lung cancer cell survival, growth, and migration.
Article in Cancer science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 83 citations in OpenAlex.
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- Identifying the potential anti-lung cancer targets of Baicalein using a network pharmacology approach.Scientific reports · 2026Article
- Paeonol protects against cisplatin-induced premature ovarian failure via anti-inflammatory and antioxidant activities: an integrated approach of network pharmacology, molecular dynamics simulation, and experimental validation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Mechanistic insights into DEHP-induced progression of non-small cell lung cancer based on network toxicology and molecular docking.Scientific reports · 2025Article
- Article
- SREBP-2 promotes cancer progression through the mevalonate-Akt pathway in non-small cell lung cancer.Scientific reports · 2025Article
- Article
- Anticancer Effects of Mitoquinone via Cell Cycle Arrest and Apoptosis in Canine Mammary Gland Tumor Cells.International journal of molecular sciences · 2024Article
- Targeted Inhibition of Hsp90 in Combination with Metformin Modulates Programmed Cell Death Pathways in A549 Lung Cancer Cells.Applied biochemistry and biotechnology · 2023Article
- Computational drug repurposing of Akt-1 allosteric inhibitors for non-small cell lung cancer.Scientific reports · 2023Article
- The ethyl acetate extract of Wenxia Changfu Formula inhibits the carcinogenesis of lung adenocarcinoma by regulating PI3K-AKT signaling pathway.Scientific reports · 2023Article
- Nuclear accumulation of KPNA2 impacts radioresistance through positive regulation of the PLSCR1-STAT1 loop in lung adenocarcinoma.Cancer science · 2022Article
- Crosstalk between protein kinases AKT and ERK1/2 in human lung tumor-derived cell models.Frontiers in oncology · 2022Article
- Semaphorin 4D is a potential biomarker in pediatric leukemia and promotes leukemogenesis by activating PI3K/AKT and ERK signaling pathways.Oncology reports · 2021Article
- Uncovering the Anti-Lung-Cancer Mechanisms of the Herbal Drug FDY2004 by Network Pharmacology.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- An ApoA-I Mimic Peptide of 4F Promotes SDF-1α Expression in Endothelial Cells Through PI3K/Akt/ERK/HIF-1α Signaling Pathway.Frontiers in pharmacology · 2021Article
- EXP2SL: A Machine Learning Framework for Cell-Line-Specific Synthetic Lethality Prediction.Frontiers in pharmacology · 2020Article
- Distinct functions of AKT isoforms in breast cancer: a comprehensive review.Cell communication and signaling : CCS · 2019Review
- Transcriptomic analysis associated with reversal of cisplatin sensitivity in drug resistant osteosarcoma cells after a drug holiday.BMC cancer · 2019Article
- RBAK is upregulated in non-small cell lung cancer and promotes cell migration and invasion.Experimental and therapeutic medicine · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although AKT ⁄ protein kinase B is constitutively active in nonsmall cell lung cancer (NSCLC) cells and is an attractive target for enhancing the cytotoxicity of therapeutic agents, the distinct roles of the AKT isoforms in NSCLC are largely unknown. In the present study, we investigated the roles of AKT1 and AKT2 in NSCLC cells using RNAi. The siRNA targeting of AKT1 or AKT2 effectively decreased protein levels of AKT1 and AKT2, respectively, in A549 and H460 cells. Cisplatin treatment of these cells increased apoptotic cell death compared with control. The siRNA-induced knockdown of AKT1 in H460 cells significantly decreased basal MEK⁄ ERK1 ⁄ 2 activity, resulting in nuclear factor-κB activation, whereas knockdown of AKT2 resulted in anti-apoptotic Bcl-2 family protein MCL-1 (MCL-1) cleavage, the collapse of mitochondrial membrane potential, cytochrome c release, and activation of the caspase cascade. Consequently, both siRNA treatments enhanced the chemosensitivity of H460 cells to cisplatin. However, neither AKT1 nor AKT2 siRNA treatment had any effect of p27 expression, and although both treatments tended to induced G₂ ⁄M phase arrest, the effect was not statistically significant. Treatment with AKT1 siRNA markedly decreased colony formation growth and migration, but AKT2 siRNA had no significant effects on these parameters. These data suggest that AKT1 and AKT2 both contribute to cell survival, albeit via different mechanisms, and that the effects on cell growth and migration are predominantly regulated by AKT1. These findings may aid in refining targeted strategies for the inhibition of AKT isoforms towards the sensitization of NSCLC cells to therapeutic agents.
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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.