ArticleCell death & disease2024
PIM1 kinase promotes EMT-associated osimertinib resistance via regulating GSK3β signaling pathway in EGFR-mutant non-small cell lung cancer.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The trial behind it
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Who cites it
18 citing papers in PubMed.
- PIM1-mediated signalling as a therapeutic target in breast cancer: repurposing venetoclax for targeted inhibition.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- PIM1-mediated signalling as a therapeutic target in breast cancer: repurposing venetoclax for targeted inhibition.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Exploring PIM1 Kinase as a Therapeutic Target: Mechanisms and Strategies in Cancer Treatment.International journal of molecular sciences · 2026Review
- ERCC6L drives lung adenocarcinoma metastasis: a PJA2/p53 ubiquitination-dependent mechanism.Respiratory research · 2026Article
- Activation of the PI3K/AKT pathway by EDIL3 induces EMT and promotes tumor progression in clear cell renal cell carcinoma.Molecular genetics and genomics : MGG · 2026Article
- The STAT3-ZEB1 axis contributes to CCL2-mediated resistance to osimertinib in lung cancer.Frontiers in oncology · 2026Article
- Restoring osimertinib sensitivity in EGFR-mutant NSCLC: the role of anlotinib in modulating Wnt/β-catenin/YAP pathways.American journal of cancer research · 2026Article
- Advances in understanding the mechanisms underlying acquired resistance to third-generation tyrosine kinase inhibitors in non-small cell lung cancer.Frontiers in cell and developmental biology · 2026Review
- In Silico Identification of Lepiotaprocerin C as a Promising PIM-1 Kinase Inhibitor: An Integrated Docking, Molecular Dynamics, MM/PBSA, QSAR, and ADMET Study.Bioinformatics and biology insights · 2026Article
- Advances in Targeting Growth Factor Signalling in Neuroblastoma and Overcoming Drug Resistance.Cells · 2025Review
- Long non-coding RNA AFAP1-AS1 promotes alternative splicing of AXIN2 by facilitating SRSFs phase separation to induce drug resistance in lung adenocarcinoma.Molecular cancer · 2025Article
- WNT signaling in cancer: molecular mechanisms and potential therapies.Molecular biomedicine · 2025Review
- PIM1 Attenuates Innate Immunity to Foster Coronavirus Replication through Ubiquitin Ligase β-TrCP-Mediated IFNAR1 Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Strategies Beyond 3rd EGFR-TKI Acquired Resistance: Opportunities and Challenges.Cancer medicine · 2025Review
- [Epithelial-mesenchymal Transition: Biological Basis and Clinical Prospects of Lung Cancer Invasion, Metastasis, and Drug Resistance].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Anlotinib enhances the anti-tumor activity of osimertinib in patients with non-small cell lung cancer by reversing drug resistance.Translational lung cancer research · 2025Article
- Osimertinib acquired resistance among patients with EGFR-mutated NSCLC: from molecular mechanisms to clinical therapeutic strategies.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- GSK3β serves as a novel therapeutic target in patients with type 2 diabetes mellitus complicated by colorectal cancer.American journal of translational research · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Acquired resistance is inevitable in the treatment of non-small cell lung cancer (NSCLC) with osimertinib, and one of the primary mechanisms responsible for this resistance is the epithelial-mesenchymal transition (EMT). We identify upregulation of the proviral integration site for Moloney murine leukemia virus 1 (PIM1) and functional inactivation of glycogen synthase kinase 3β (GSK3β) as drivers of EMT-associated osimertinib resistance. Upregulation of PIM1 promotes the growth, invasion, and resistance of osimertinib-resistant cells and is significantly correlated with EMT molecules expression. Functionally, PIM1 suppresses the ubiquitin-proteasome degradation of snail family transcriptional repressor 1 (SNAIL) and snail family transcriptional repressor 2 (SLUG) by deactivating GSK3β through phosphorylation. The stability and accumulation of SNAIL and SLUG facilitate EMT and encourage osimertinib resistance. Furthermore, treatment with PIM1 inhibitors prevents EMT progression and re-sensitizes osimertinib-resistant NSCLC cells to osimertinib. PIM1/GSK3β signaling is activated in clinical samples of osimertinib-resistant NSCLC, and dual epidermal growth factor receptor (EGFR)/PIM1 blockade synergistically reverse osimertinib-resistant NSCLC in vivo. These data identify PIM1 as a driver of EMT-associated osimertinib-resistant NSCLC cells and predict that PIM1 inhibitors and osimertinib combination therapy will provide clinical benefit in patients with EGFR-mutant 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 Socratic graph.