ArticleOncotarget2016
Oncogenic ALK regulates EMT in non-small cell lung carcinoma through repression of the epithelial splicing regulatory protein 1.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- ALK rearrangements and resistance mutations in non-small cell lung cancer: molecular mechanisms and therapeutic implications.Cancer chemotherapy and pharmacology · 2026Review
- E-cadherin-driven adherens junction reinforcement promotes spheroid-mediated invasion and progression in ALK-rearranged lung cancer chemoresistance.Molecules and cells · 2026Article
- CXCR4-LASP1-G9a-SNAIL axis drives NEPC transdifferentiation via induction of EMT and downregulation of REST.Cell genomics · 2025Article
- ALK in cancer: from function to therapeutic targeting.Nature reviews. Cancer · 2025Review
- Article
- Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.Journal of hematology & oncology · 2025Review
- MicroRNAs as the critical regulators of epithelial mesenchymal transition in pancreatic tumor cells.Heliyon · 2024Review
- Article
- Downregulated ESRP1/2 promotes lung metastasis of bladder carcinoma through altering FGFR2 splicing and macrophage polarization.Frontiers in immunology · 2023Article
- Silibinin Overcomes EMT-Driven Lung Cancer Resistance to New-Generation ALK Inhibitors.Cancers · 2022Article
- Underlying mechanisms of epithelial splicing regulatory proteins in cancer progression.Journal of molecular medicine (Berlin, Germany) · 2022Review
- EML4-ALK fusion gene in non-small cell lung cancer.Oncology letters · 2022Review
- HER3 activation contributes toward the emergence of ALK inhibitor-tolerant cells in ALK-rearranged lung cancer with mesenchymal features.NPJ precision oncology · 2022Article
- Hexokinases II-mediated glycolysis governs susceptibility to crizotinib in ALK-positive non-small cell lung cancer.Thoracic cancer · 2021Article
- Article
- Discohesive growth pattern (Disco-p) as an unfavorable prognostic factor in lung adenocarcinoma: an analysis of 1062 Japanese patients with resected lung adenocarcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Article
- Acquired resistance to targeted therapies in NSCLC: Updates and evolving insights.Pharmacology & therapeutics · 2020Review
- Proteomics-Based Evidence for a Pro-Oncogenic Role of ESRP1 in Human Colorectal Cancer Cells.International journal of molecular sciences · 2020Article
- A lab-on-a-disc platform enables serial monitoring of individual CTCs associated with tumor progression during EGFR-targeted therapy for patients with NSCLC.Theranostics · 2020Article
- Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
A subset of Non-Small Cell Lung Carcinoma (NSCLC) carries chromosomal rearrangements involving the Anaplastic Lymphoma Kinase (ALK) gene. ALK-rearranged NSCLC are typically adenocarcinoma characterized by a solid signet-ring cell pattern that is frequently associated with a metastatic phenotype. Recent reports linked the presence of ALK rearrangement to an epithelial-mesenchymal transition (EMT) phenotype in NSCLC, but the extent and the mechanisms of an ALK-mediated EMT in ALK-rearranged NSCLC are largely unknown. We found that the ALK-rearranged H2228 and DFCI032, but not the H3122, cell lines displayed a mesenchymal phenotype. In these cell lines, oncogenic ALK activity dictated an EMT phenotype by directly suppressing E-cadherin and up-regulating vimentin expression, as well as expression of other genes involved in EMT. We found that the epithelial splicing regulatory protein 1 (ESRP1), a key regulator of the splicing switch during EMT, was repressed by EML4-ALK activity. The treatment of NSCLC cells with ALK tyrosine kinase inhibitors (TKIs) led to up-regulation of ESRP1 and E-cadherin, thus reverting the phenotype from mesenchymal to epithelial (MET). Consistently, ESRP1 knock-down impaired E-cadherin up-regulation upon ALK inhibition, whereas enforced expression of ESRP1 was sufficient to increase E-cadherin expression. These findings demonstrate an ALK oncogenic activity in the regulation of an EMT phenotype in a subset of NSCLC with potential implications for the biology of ALK-rearranged NSCLC in terms of metastatic propensity and resistance to 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.