ArticleMolecular oncology2013
Nelfinavir and bortezomib inhibit mTOR activity via ATF4-mediated sestrin-2 regulation.
Article in Molecular oncology, 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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Who cites it
79 citing papers in PubMed, 138 citations in OpenAlex.
- MITF, TFEB, and TFE3 drive distinct adaptive gene expression programs and immune infiltration in melanoma.Cell reports · 2025Article
- Sestrin2 is Induced Upon Cellular Stress but Has No Effect on Myotube Size or Amino Acid Sensing in C2C12 Myotubes.Biology of the cell · 2025Article
- Nelfinavir triggers ferroptosis by inducing ER stress mediated downregulation of GPX4/GSH system, upregulation of NRF2/HO-1 axis, and mitochondrial impairment in hepatocellular carcinoma cells.Cell death discovery · 2025Article
- Lysosomal reduced thiols are essential for mouse embryonic development.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Artemisinin synergizes with CCCP in autophagic cell death induction via ER stress in uveal melanoma.iScience · 2025Article
- Review
- CRISPuRe-seq: pooled screening of barcoded ribonucleoprotein reporters reveals regulation of RNA polymerase III transcription by the integrated stress response via mTOR.Nucleic acids research · 2025Article
- BAG3 Mediated Down-regulation in Expression of p66shc has Ramifications on Cellular Proliferation, Apoptosis and Metastasis.Cell biochemistry and biophysics · 2024Article
- Ubiquitination regulates autophagy in cancer: simple modifications, promising targets.Journal of translational medicine · 2024Review
- DNA methylation-driven gene FAM3D promotes colorectal cancer growth via the ATF4-SESN2-mTORC1 pathway.Aging · 2024Article
- Sestrin2 drives ER-phagy in response to protein misfolding.Developmental cell · 2024Article
- Antiretroviral Drugs Impact Autophagy: Opportunities for Drug Repurposing.Frontiers in bioscience (Landmark edition) · 2024Review
- Sublethal engagement of apoptotic pathways in residual cancer.Trends in cell biology · 2024Review
- ATF4 Signaling in HIV-1 Infection: Viral Subversion of a Stress Response Transcription Factor.Biology · 2024Review
- Role of sestrins in metabolic and aging-related diseases.Biogerontology · 2024Review
- Antioxidant genes in cancer and metabolic diseases: Focusing on Nrf2, Sestrin, and heme oxygenase 1.International journal of biological sciences · 2024Review
- Insights into the molecular underlying mechanisms and therapeutic potential of endoplasmic reticulum stress in sensorineural hearing loss.Frontiers in molecular neuroscience · 2024Review
- The role of autophagy in hypoxia-induced radioresistance.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2023Review
- Article
- Inhibition of the NOTCH and mTOR pathways by nelfinavir as a novel treatment for T cell acute lymphoblastic leukemia.International journal of oncology · 2023Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum (ER) stress and autophagy are two basic cell survival mechanisms often occurring in concert. Extensive ER stress in cancer cells deliberately induced by chemotherapeutic drugs may lead to growth arrest and cell death. However, the link between ER stress and autophagy is not well understood. In this study, the treatment of cancer cells with ER stress-inducing drug nelfinavir resulted in the expression of endogenous mTOR inhibitor sestrin-2 (SESN2). Upregulation of SESN2 expression was associated with expression of ER stress markers ATF4, ATF3, and CHOP. SESN2 upregulation also occurred in cells treated with the proteasome inhibitor bortezomib. Ectopic expression of ATF4, but not of ATF3 or CHOP, caused transcriptional upregulation of SESN2 expression, indicating expressional regulation of SESN2 by ATF4. Transient overexpression of ectopic SESN2 resulted in mTOR inhibition and autophagy, confirming a link between ER stress, SESN2 upregulation, and mTOR inhibition. Accordingly, cancer cells treated with the ER stress-inducing agent nelfinavir showed reduced mTOR activity and associated increases in the expression levels of ATF4 and SESN2. These results show that ATF4-regulated SESN2 expression presents a new link between ER stress and mTOR inhibition and autophagy. mTOR inhibition by nelfinavir, which is currently in clinical trials for cancer patients, may also explain its observed ability to induce autophagy, growth arrest, and radiosensitization in cancer cells.
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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.