ArticleNeoplasia (New York, N.Y.)2011
Ras-related tumorigenesis is suppressed by BNIP3-mediated autophagy through inhibition of cell proliferation.
Article in Neoplasia (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 77 citations in OpenAlex.
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- Inhibition of autophagy as a novel treatment for neurofibromatosis type 1 tumors.Molecular oncology · 2025Article
- The impact of evodiamine on human anaplastic thyroid cancer therapy-anInternational journal of medical sciences · 2025Article
- Increased autophagy activity suppresses hyperglycemia-related colorectal cancer tumorigenesis bothAmerican journal of cancer research · 2025Article
- The role and regulatory mechanism of lysosome associated protein transmembrane 4β in tumors.Frontiers in oncology · 2025Review
- The role of Atg5 gene in tumorigenesis under autophagy deficiency conditions.The Kaohsiung journal of medical sciences · 2024Article
- Role and mechanism of action of LAPTM4B in EGFR-mediated autophagy.Oncology letters · 2022Review
- RAS-mediated tumor stress adaptation and the targeting opportunities it presents.Disease models & mechanisms · 2022Article
- Role of RAS signaling in ovarian cancer.F1000Research · 2022Review
- Bcl-2 Interacts with Beclin 1 and Regulates Autophagy in 7, 12-Dimethylbenz[a]anthracene-Induced Hamster Buccal-Pouch Squamous-Cell Tumorigenesis.Current medical science · 2021Article
- EBV-LMP1 promotes radioresistance by inducing protective autophagy through BNIP3 in nasopharyngeal carcinoma.Cell death & disease · 2021Article
- Prognostic Signature of Osteosarcoma Based on 14 Autophagy-Related Genes.Pathology oncology research : POR · 2021Article
- PIWIL1 Drives Chemoresistance in Multiple Myeloma by Modulating Mitophagy and the Myeloma Stem Cell Population.Frontiers in oncology · 2021Article
- Autophagy Upregulates miR-449a Expression to Suppress Progression of Colorectal Cancer.Frontiers in oncology · 2021Article
- Inhibition of Calcineurin/NFAT Signaling Blocks Oncogenic H-Ras Induced Autophagy in Primary Human Keratinocytes.Frontiers in cell and developmental biology · 2021Article
- Saponin Formosanin C-induced Ferritinophagy and Ferroptosis in Human Hepatocellular Carcinoma Cells.Antioxidants (Basel, Switzerland) · 2020Article
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8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy plays diverse roles in Ras-related tumorigenesis. H-ras(val12) induces autophagy through multiple signaling pathways including Raf-1/ERK pathway, and various ERK downstream molecules of autophagy have been reported. In this study, Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) is identified as a downstream transducer of the Ras/Raf/ERK signaling pathway to induce autophagy. BNIP3 was upregulated by H-ras(val12) at the transcriptional level to compete with Beclin 1 for binding with Bcl-2. H-ras(val12)-induced autophagy suppresses cell proliferation demonstrated both in vitro and in vivo by expression of ectopic BNIP3, Atg5, or interference RNA of BNIP3 (siBNIP3) and Atg5 (shAtg5) using mouse NIH3T3 and embryo fibroblast cells. H-ras(val12) induces different autophagic responses depending on the duration of Ras overexpression. After a short time (48 hours) of Ras overexpression, autophagy inhibits cell proliferation. In contrast, a longer time (2 weeks) of Ras overexpression, cell proliferation was enhanced by autophagy. Furthermore, overexpression of mutant Ras, BNIP3, and LC3-II was detected in bladder cancer T24 cells and the tumor parts of 75% of bladder cancer specimens indicating a positive correlation between autophagy and tumorigenesis. Taken together, our mouse model demonstrates a balance between BNIP3-mediated autophagy and H-ras(val12)-induced tumor formation and reveals that H-ras(val12) induces autophagy in a BNIP3-dependent manner, and the threshold of autophagy plays a decisive role in H-ras(val12)-induced tumorigenesis. Our findings combined with others' reports suggest a new therapeutic strategy against Ras-related tumorigenesis by negative or positive regulation of autophagic activity, which is determined by the level of autophagy and tumor progression stages.
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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.