ArticleScience signaling2013
PUMA and BIM are required for oncogene inactivation-induced apoptosis.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
79 citing papers in PubMed, 123 citations in OpenAlex.
- Article
- Pharmaco-genomic characterization of pancreatic and biliary tract cancer tumoroids for drug response.iScience · 2026Article
- The emerging role of exosomal circRNAs in modulating apoptotic pathways and overcoming cancer therapy resistance.Discover oncology · 2026Review
- The multifaceted role of PUMA in cell death pathways: its therapeutic potential across cancer types.Cell communication and signaling : CCS · 2025Review
- Anoikis resistance in gastric cancer: a comprehensive review.Cell death & disease · 2025Review
- Repurposing of triamterene as a histone deacetylase inhibitor to overcome cisplatin resistance in lung cancer treatment.Journal of cancer research and clinical oncology · 2023Article
- Potential Chemopreventive Role of Pterostilbene in Its Modulation of the Apoptosis Pathway.International journal of molecular sciences · 2023Review
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Caspase 3-specific cleavage of MEK1 suppresses ERK signaling and sensitizes cells to stress-induced apoptosis.FEBS open bio · 2023Article
- FOXO nuclear shuttling dynamics are stimulus-dependent and correspond with cell fate.Molecular biology of the cell · 2023Article
- Article
- Identification ofInternational journal of molecular sciences · 2022Article
- Chidamide and venetoclax synergistically exert cytotoxicity on multiple myeloma by upregulating BIM expression.Clinical epigenetics · 2022Article
- Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy.Cell death & disease · 2022Article
- The manipulation of apoptosis for cancer therapy using BH3-mimetic drugs.Nature reviews. Cancer · 2022Review
- miR-221 confers lapatinib resistance by negatively regulating p27Cancer science · 2021Article
- Targeting Aurora B kinase prevents and overcomes resistance to EGFR inhibitors in lung cancer by enhancing BIM- and PUMA-mediated apoptosis.Cancer cell · 2021Article
- Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics.Biomolecules · 2021Review
- A carbazole compound, 9-ethyl-9H-carbazole-3-carbaldehyde, plays an antitumor function through reactivation of the p53 pathway in human melanoma cells.Cell death & disease · 2021Article
- FLT3 tyrosine kinase inhibitors synergize with BCL-2 inhibition to eliminate FLT3/ITD acute leukemia cells through BIM activation.Signal transduction and targeted therapy · 2021Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The clinical efficacy of tyrosine kinase inhibitors supports the dependence of distinct subsets of cancers on specific driver mutations for survival, a phenomenon called "oncogene addiction." We demonstrate that PUMA and BIM are the key apoptotic effectors of tyrosine kinase inhibitors in breast cancers with amplification of the gene encoding human epidermal growth factor receptor 2 (HER2) and lung cancers with epidermal growth factor receptor (EGFR) mutants. The BH3 domain containing proteins BIM and PUMA can directly activate the proapoptotic proteins BAX and BAK to permeabilize mitochondria, leading to caspase activation and apoptosis. We delineated the signal transduction pathways leading to the induction of BIM and PUMA by tyrosine kinase inhibitors. Inhibition of the mitogen-activated or extracellular signal-regulated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway caused increased abundance of BIM, whereas antagonizing the phosphoinositide 3-kinase (PI3K)-AKT pathway triggered nuclear translocation of the FOXO transcription factors, which directly activated the PUMA promoter. In a mouse breast tumor model, the abundance of PUMA and BIM was increased after inactivation of HER2. Moreover, deficiency of Bim or Puma impaired caspase activation and reduced tumor regression caused by inactivation of HER2. Similarly, deficiency of Puma impeded the regression of EGFR(L858R)-driven mouse lung tumors upon inactivation of the EGFR-activating mutant. Overall, our study identified PUMA and BIM as the sentinels that interconnect kinase signaling networks and the mitochondrion-dependent apoptotic program, which offers therapeutic insights for designing novel cell death mechanism-based anticancer strategies.
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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.