ArticleCancer science2018
Hypoxia-inducible transgelin 2 selects epithelial-to-mesenchymal transition and γ-radiation-resistant subtypes by focal adhesion kinase-associated insulin-like growth factor 1 receptor activation in non-small-cell lung cancer cells.
Article in Cancer science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
- Hypoxia/Reoxygenation-Induced Mitochondrial Reverse Electron Transfer: A Targetable Mechanism to Enhance Radiosensitivity in Non-Small Cell Lung Cancer.Antioxidants (Basel, Switzerland) · 2026Article
- A novel TM4SF4-targeting therapeutic antibody candidate with antitumor activity by blocking IGF1R and CD44 signaling and downregulating PD-L1 and B7-H4.Theranostics · 2026Article
- Gastrodin reduces myocardial ischemia/reperfusion injury via transgelin2/CNPase-mediated apoptosis regulation.Frontiers in pharmacology · 2025Article
- Robust self-supervised learning strategy to tackle the inherent sparsity in single-cell RNA-seq data.Briefings in bioinformatics · 2024Article
- Feedback loop between hypoxia and energy metabolic reprogramming aggravates the radioresistance of cancer cells.Experimental hematology & oncology · 2024Review
- Single-cell RNA sequencing reveals the lineage of malignant epithelial cells and upregulation of TAGLN2 promotes peritoneal metastasis in gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Molecular signaling network and therapeutic developments in breast cancer brain metastasis.Advances in cancer biology - metastasis · 2023Article
- An Integrated Analysis Identified TAGLN2 As an Oncogene Indicator Related to Prognosis and Immunity in Pan-Cancer.Journal of Cancer · 2023Article
- TAGLN2-Regulated Trophoblast Migration, Invasion and Fusion are Impaired in Preeclampsia.Frontiers in cell and developmental biology · 2022Article
- Cannabinoid receptors promote chronic intermittent hypoxia-induced breast cancer metastasis via IGF-1R/AKT/GSK-3β.Molecular therapy oncolytics · 2021Article
- MiR-613 inhibits the proliferation, migration, and invasion of papillary thyroid carcinoma cells by directly targeting TAGLN2.Cancer cell international · 2021Article
- Bioinformatics analysis reveals the roles of cytoskeleton protein transgelin in occurrence and development of proteinuria.Translational pediatrics · 2021Article
- Review
- Alterations in the Global Proteome and Phosphoproteome in Third Generation EGFR TKI Resistance Reveal Drug Targets to Circumvent Resistance.Cancer research · 2021Article
- Hypoxia Transcriptomic Modifications Induced by Proton Irradiation in U87 Glioblastoma Multiforme Cell Line.Journal of personalized medicine · 2021Article
- Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing.Cancers · 2021Review
- An Essential NRP1-Mediated Role for Tagln2 in Gastric Cancer Angiogenesis.Frontiers in oncology · 2021Article
- Acupuncture Regulates Serum Differentially Expressed Proteins in Patients with Chronic Atrophic Gastritis: A Quantitative iTRAQ Proteomics Study.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Transgelin-2: A Double-Edged Sword in Immunity and Cancer Metastasis.Frontiers in cell and developmental biology · 2021Review
- jouvence, a new human snoRNA involved in the control of cell proliferation.BMC genomics · 2020Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Microenvironment, such as hypoxia common to cancer, plays a critical role in the epithelial-to-mesenchymal transition (EMT) program, which is a major route of cancer metastasis and confers γ-radiation resistance to cells. Herein, we showed that transgelin 2 (TAGLN2), an actin-binding protein, is significantly induced in hypoxic lung cancer cells and that Snail1 is simultaneously increased, which induces EMT by downregulating E-cadherin expression. Forced TAGLN2 expression induced severe cell death; however, a small population of cells surviving after forced TAGLN2 overexpression showed γ-radiation resistance, which might promote tumor relapse and recurrence. These surviving cells showed high metastatic activity with an increase of EMT markers including Snail1. In these cells, TAGLN2 activated the insulin-like growth factor 1 receptor β (IGF1Rβ)/PI3K/AKT pathway by recruitment of focal adhesion kinase to the IGF1R signaling complex. Activation of the IGF1Rβ/PI3K/AKT pathway also induced inactivation of glycogen synthase kinase 3β (GSK3β), which is involved in Snail1 stabilization. Therefore, both the IGF1Rβ inhibitor (AG1024) and the PI3K inhibitor (LY294002) or AKT inactivation with MK2206 lower the cellular level of Snail1. Involvement of GSK3β was also confirmed by treatment with lithium chloride, the inducer of GSK3β phosphorylation, or MG132, the 26S proteasomal inhibitor, which also stabilized Snail1. In conclusion, the present study provides important evidence that hypoxia-inducible TAGLN2 is involved in the selection of cancer cells with enhanced EMT properties to overcome the detrimental environment of cancer cells.
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