ArticleSignal transduction and targeted therapy2022
Elaiophylin triggers paraptosis and preferentially kills ovarian cancer drug-resistant cells by inducing MAPK hyperactivation.
Article in Signal transduction and targeted therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 4 of them syntheses that pooled it.
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Who cites it
62 citing papers in PubMed, 4 syntheses or guidelines pooled it, 93 citations in OpenAlex.
- The interaction between endoplasmic reticulum stress and ferroptosis in ovarian diseases.Journal of ovarian research · 2026Pooled it
- Global research landscape and hotspots of paraptosis: a multi-database bibliometric analysis with a focused literature review.Frontiers in oncology · 2026Pooled it
- Unraveling the role of M2 TAMs in ovarian cancer dynamics: a systematic review.Journal of translational medicine · 2025Pooled it
- Programmed cell death in human respiratory syncytial virus infection.Frontiers in cellular and infection microbiology · 2025Pooled it
- The P7 peptide antagonizes bFGF-induced malignant behaviors of ovarian cancer by inhibiting MEK/ERK signaling pathway.Future science OA · 2026Article
- Nutrient deprivation enhances the cytotoxic effects of a sulfonamide-chalcone hybrid in PC-3 prostate cancer cells.Molecular and cellular biochemistry · 2026Article
- MAP2K6 reprograms NADCell death & disease · 2026Article
- TUFT1 stabilizes TGF-β receptor II protein and facilitates activation of hepatic stellate cells into metastasis-promoting myofibroblasts.Cell death and differentiation · 2026Article
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting non-apoptotic regulated cell death (RCD) to treat neurodegenerative diseases.Acta pharmaceutica Sinica. B · 2026Review
- Icaritin Disrupts Cholesterol Biosynthesis and Induce Cell Death in Pancreatic Carcinoma: A Transcriptomic and Lipidomic Analysis.Chinese journal of integrative medicine · 2026Article
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- Crosstalk Between Autophagy and Paraptosis: A New Frontier in Cancer Therapy.International journal of molecular sciences · 2026Review
- Tumor cell cycle regulation: integrated perspective of stage characteristics, regulatory networks, and signaling pathway intervention strategies.Molecular biomedicine · 2026Review
- Review
- Copper-instigated modulatory cell mortality mechanisms and progress in kidney diseases.Renal failure · 2025Review
- Paraptosis-related genes regulate tumor immune microenvironment and predict prognosis in breast cancer.Journal of cell communication and signaling · 2025Article
- Ubiquitin-independent pathway regulates the RIT1-MAPK pathway in chordoma progression.Cell death & disease · 2025Article
- Guanine Nucleotide Exchange Factors and Small GTPases: Their Regulation and Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Finely tuned mitogen-activated protein kinase (MAPK) signaling is important for cancer cell survival. Perturbations that push cells out of the MAPK fitness zone result in cell death. Previously, in a screen of the North China Pharmaceutical Group Corporation's pure compound library of microbial origin, we identified elaiophylin as an autophagy inhibitor. Here, we demonstrated a new role for elaiophylin in inducing excessive endoplasmic reticulum (ER) stress, ER-derived cytoplasmic vacuolization, and consequent paraptosis by hyperactivating the MAPK pathway in multiple cancer cells. Genome-wide CRISPR/Cas9 knockout library screening identified SHP2, an upstream intermediary of the MAPK pathway, as a critical target in elaiophylin-induced paraptosis. The cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) assay further confirmed the direct binding between the SHP2 and elaiophylin. Inhibition of the SHP2/SOS1/MAPK pathway through SHP2 knockdown or pharmacological inhibitors distinctly attenuated elaiophylin-induced paraptosis and autophagy inhibition. Interestingly, elaiophylin markedly increased the already-elevated MAPK levels and preferentially killed drug-resistant cells with enhanced basal MAPK levels. Elaiophylin overcame drug resistance by triggering paraptosis in multiple tumor-bearing mouse models resistant to platinum, taxane, or PARPi, suggesting that elaiophylin might offer a reasonable therapeutic strategy for refractory ovarian cancer.
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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.