ArticleOncogene1999
Oncogenic Ras triggers cell suicide through the activation of a caspase-independent cell death program in human cancer cells.
Article in Oncogene, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 250 citations in OpenAlex.
- Metabolic cell death in cancer: mechanisms and therapeutic potential.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- Targeting macropinocytosis for cancer therapy.Nature reviews. Cancer · 2026Review
- Novel selective inhibitors of macropinocytosis-dependent growth in pancreatic ductal carcinoma.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Casein kinase 2 phosphorylates and induces the SALL2 tumor suppressor degradation in colon cancer cells.Cell death & disease · 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
- Progress in the discovery and development of small molecule methuosis inducers.RSC medicinal chemistry · 2023Review
- Surveying the landscape of emerging and understudied cell death mechanisms.Biochimica et biophysica acta. Molecular cell research · 2023Review
- Paraptosis: a unique cell death mode for targeting cancer.Frontiers in pharmacology · 2023Review
- A Mini Review on Molecules Inducing Caspase-Independent Cell Death: A New Route to Cancer Therapy.Molecules (Basel, Switzerland) · 2022Review
- Inhibition of the Phospholipase Cε-c-Jun N-Terminal Kinase Axis Suppresses Glioma Stem Cell Properties.International journal of molecular sciences · 2022Article
- The Potential of Novel Lipid Agents for the Treatment of Chemotherapy-Resistant Human Epithelial Ovarian Cancer.Cancers · 2022Review
- Revisiting Regulated Cell Death Responses in Viral Infections.International journal of molecular sciences · 2022Review
- The roles of GTPase-activating proteins in regulated cell death and tumor immunity.Journal of hematology & oncology · 2021Review
- Targeting Drug Chemo-Resistance in Cancer Using Natural Products.Biomedicines · 2021Review
- CD52 is a novel target for the treatment of FLT3-ITD-mutated myeloid leukemia.Cell death discovery · 2021Article
- The ERK mitogen-activated protein kinase signaling network: the final frontier in RAS signal transduction.Biochemical Society transactions · 2021Review
- Predicted 'wiring landscape' of Ras-effector interactions in 29 human tissues.NPJ systems biology and applications · 2021Article
- Autophagy: Mechanisms and Therapeutic Potential of Flavonoids in Cancer.Biomolecules · 2021Review
- From Pinocytosis to Methuosis-Fluid Consumption as a Risk Factor for Cell Death.Frontiers in cell and developmental biology · 2021Review
- Inhibition of Calcineurin/NFAT Signaling Blocks Oncogenic H-Ras Induced Autophagy in Primary Human Keratinocytes.Frontiers in cell and developmental biology · 2021Article
15 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
13 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To prevent neoplasia, cells of multicellular organisms activate cellular disposal programs such as apoptosis in response to deregulated oncogene expression, making the suppression of such programs an essential step for potentially neoplastic cells to become established as clinically relevant tumors. Since the mutation of ras proto-oncogenes, the most frequently mutated proto-oncogenes in human tumors, is very rare in some tumor types such as glioblastomas and gastric cancers, we hypothesized that mutated ras genes might activate a cell death program that cannot be overcome by these tumor types. Here we show that the expression of oncogenically mutated ras gene induces cellular degeneration accompanied by cytoplasmic vacuoles in human glioma and gastric cancer cell lines. Cells dying as a result of oncogenic Ras expression had relatively well-preserved nuclei that were negative for TUNEL staining. An immunocytochemical analysis demonstrated that the cytoplasmic vacuoles are derived mainly from lysosomes. This oncogenic Ras-induced cell death occurred in the absence of caspase activation, and was not inhibited by the overexpression of anti-apoptotic Bcl-2 protein. These observations suggested that oncogenic Ras-induced cell death is most consistent with a type of programmed cell death designated 'type 2 physiological cell death' or 'autophagic degeneration', and that this cell death is regulated by a molecular mechanism distinct from that of apoptosis. Our findings suggest a possible role for this non-apoptotic cell death in the prevention of neoplasia, and the activation of the non-apoptotic cell death program may become a potential cancer therapy complementing apoptosis-based therapies. In addition, the approach used in this study may be a valuable way to find genetically-regulated cell suicide programs that cannot be overcome by particular tumor types.
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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.