ArticleCell reports2021
TIAM1-RAC1 promote small-cell lung cancer cell survival through antagonizing Nur77-induced BCL2 conformational change.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- RAC1 signaling in polyploid giant cancer cells: Implications for tumorigenesis and therapy resistance.Cancer letters · 2026Review
- CSDE1 Drives Glycolysis and the Progression of Prostate Cancer Through RAC1-Dependent RAS/MAPK Activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The GAP43/RAC1 axis drives glycolytic reprogramming and progression in lung adenocarcinoma.Respiratory research · 2026Article
- Rac1 in gastric cancer: a molecular driver of invasion, EMT, and therapeutic resistance.Journal of translational medicine · 2025Review
- Adaptation to Volumetric Compression Drives an Apoptosis-Resistant and Invasive Phenotype in Liver Cancer.Cancer research · 2025Article
- RNA Sequencing Reveals Inflammatory and Metabolic Changes in the Lung and Brain After Carbon Black and Naphthalene Whole Body Inhalation Exposure in a Rodent Model of Military Burn Pit Exposures.International journal of molecular sciences · 2025Article
- Controversy and multiple roles of the solitary nucleus receptor Nur77 in disease and physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Metastatic sites, prognosis, and a new nomogram for predicting overall survival among small cell lung cancer patients with liver metastasis: a retrospective study based on SEER.Journal of thoracic disease · 2025Article
- Functional Changes Associated With the Subcellular Localization of the Nuclear Receptor NR4A1.Biochemistry research international · 2025Review
- Discovery of a novel exceptionally potent and orally active Nur77 ligand NB1 with a distinct binding mode for cancer therapy.Acta pharmaceutica Sinica. B · 2024Article
- Therapeutic targeting ERRγ suppresses metastasis via extracellular matrix remodeling in small cell lung cancer.EMBO molecular medicine · 2024Article
- Photoactivatable Nanobody Conjugate Dimerizer Temporally Resolves Tiam1-Rac1 Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- miR-590-5p/Tiam1-mediated glucose metabolism promotes malignant evolution of pancreatic cancer by regulating SLC2A3 stability.Cancer cell international · 2023Article
- Effects of S-Adenosylhomocysteine Hydrolase Downregulation on Wnt Signaling Pathway in SW480 Cells.International journal of molecular sciences · 2023Article
- A TIAM1-TRIM28 complex mediates epigenetic silencing of protocadherins to promote migration of lung cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Rac1: A Regulator of Cell Migration and a Potential Target for Cancer Therapy.Molecules (Basel, Switzerland) · 2023Review
- Zkscan3 affects erythroblast development by regulating the transcriptional activity of GATA1 and KLF1 in mice.Journal of molecular histology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Small-cell lung cancer (SCLC), an aggressive neuroendocrine malignancy, has limited treatment options beyond platinum-based chemotherapy, whereafter acquired resistance is rapid and common. By analyzing expression data from SCLC tumors, patient-derived models, and established cell lines, we show that the expression of TIAM1, an activator of the small GTPase RAC1, is associated with a neuroendocrine gene program. TIAM1 depletion or RAC1 inhibition reduces viability and tumorigenicity of SCLC cells by increasing apoptosis associated with conversion of BCL2 from its pro-survival to pro-apoptotic function via BH3 domain exposure. This conversion is dependent upon cytoplasmic translocation of Nur77, an orphan nuclear receptor. TIAM1 interacts with and sequesters Nur77 in SCLC cell nuclei and TIAM1 depletion or RAC1 inhibition promotes Nur77 translocation to the cytoplasm. Mutant TIAM1 with reduced Nur77 binding fails to suppress apoptosis triggered by TIAM1 depletion. In conclusion, TIAM1-RAC1 signaling promotes SCLC cell survival via Nur77 nuclear sequestration.
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Registered trials
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