ArticleMolecular cancer research : MCR2010
Induction of nonapoptotic cell death by activated Ras requires inverse regulation of Rac1 and Arf6.
Article in Molecular cancer research : MCR, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 99 citations in OpenAlex.
- Metabolic hallmarks of regulated cell death.Cell research · 2026Review
- Pictilisib and nutrient stress synergize to induce methuosis via PI(4,5)PCell death & disease · 2026Article
- Review
- Reactive Oxygen Species Across Death Pathways: Gatekeepers of Apoptosis, Ferroptosis, Pyroptosis, Paraptosis, and Beyond.International journal of molecular sciences · 2025Review
- Methuosis key gene ARF6 as a diagnostic, prognostic and immunotherapeutic marker for prostate cancer: based on a comprehensive pan-cancer multi-omics analysis.Discover oncology · 2025Article
- Comprehensive landscape of cell death mechanisms: from molecular cross-talk to therapeutic innovation in oncology.Frontiers in cell and developmental biology · 2025Review
- Matrine induces V-ATPase-dependent cytoplasmic vacuolation and inhibits the function of the lysosome in leukemia cells.Pharmaceutical science advances · 2024Article
- Exploring paraptosis as a therapeutic approach in cancer treatment.Journal of biomedical science · 2024Review
- Forms of Non-Apoptotic Cell Death and Their Role in Gliomas-Presentation of the Current State of Knowledge.Biomedicines · 2024Review
- Cellular Regulation of Macropinocytosis.International journal of molecular sciences · 2024Review
- Infection of tumor cells withPNAS nexus · 2024Article
- Nutlin-3a induces KRAS mutant/p53 wild type lung cancer specific methuosis-like cell death that is dependent on GFPT2.Journal of experimental & clinical cancer research : CR · 2023Article
- Types of Cell Death from a Molecular Perspective.Biology · 2023Review
- Progress in the discovery and development of small molecule methuosis inducers.RSC medicinal chemistry · 2023Review
- Diversity and complexity of cell death: a historical review.Experimental & molecular medicine · 2023Review
- Surveying the landscape of emerging and understudied cell death mechanisms.Biochimica et biophysica acta. Molecular cell research · 2023Review
- Inhibition of Macropinocytosis Enhances the Sensitivity of Osteosarcoma Cells to Benzethonium Chloride.Cancers · 2023Article
- Anti-c-MET Fab-Grb2-Gab1 Fusion Protein-Mediated Interference of c-MET Signaling Pathway Induces Methuosis in Tumor Cells.International journal of molecular sciences · 2022Article
- The autophagy inducer trehalose stimulates macropinocytosis in NF1-deficient glioblastoma cells.Cancer cell international · 2022Article
- Revisiting Regulated Cell Death Responses in Viral Infections.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Methuosis is a unique form of nonapoptotic cell death triggered by alterations in the trafficking of clathrin-independent endosomes, ultimately leading to extreme vacuolization and rupture of the cell. Methuosis can be induced in glioblastoma cells by expression of constitutively active Ras. This study identifies the small GTPases, Rac1 and Arf6, and the Arf6 GTPase-activating protein, GIT1, as key downstream components of the signaling pathway underlying Ras-induced methuosis. The extent to which graded expression of active H-Ras(G12V) triggers cytoplasmic vacuolization correlates with the amount of endogenous Rac1 in the active GTP state. Blocking Rac1 activation with the specific Rac inhibitor, EHT 1864, or coexpression of dominant-negative Rac1(T17N), prevents the accumulation of vacuoles induced by H-Ras(G12V). Coincident with Rac1 activation, H-Ras(G12V) causes a decrease in the amount of active Arf6, a GTPase that functions in the recycling of clathrin-independent endosomes. The effect of H-Ras(G12V) on Arf6 is blocked by EHT 1864, indicating that the decrease in Arf6-GTP is directly linked to the activation of Rac1. Constitutively active Rac1(G12V) interacts with GIT1 in immunoprecipitation assays. Ablation of GIT1 by short hairpin RNA prevents the decrease in active Arf6, inhibits vacuolization, and prevents loss of cell viability in cells expressing Rac1(G12V). Together, the results suggest that perturbations of endosome morphology associated with Ras-induced methuosis are due to downstream activation of Rac1 combined with reciprocal inactivation of Arf6. The latter seems to be mediated through Rac1 stimulation of GIT1. Further insights into this pathway could suggest opportunities for the induction of methuosis in cancers that are resistant to apoptotic cell death.
Indexed as
Identifiers
What OpenQuestion holds
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.