ArticleCell2015
MEK guards proteome stability and inhibits tumor-suppressive amyloidogenesis via HSF1.
Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
What it found
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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.
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Who cites it
96 citing papers in PubMed, 174 citations in OpenAlex.
- Trial
- Anesthetic-chemotherapy interplay in osteosarcoma: preliminary investigations with in vitro models.BMC cancer · 2026Article
- Endoplasmic reticulum stress in brain metastatic cascade.NPJ precision oncology · 2026Review
- Reprogramming gut microenvironment for the treatment of acute severe ulcerative colitis via a synergistic therapy of necroptosis blockade and organoid transplantation.Nature communications · 2026Article
- c-MYC is an aggregation-prone, amyloidogenic protein.bioRxiv : the preprint server for biology · 2026Article
- Driving proteomic imbalance in malignancy provokes proteomic catastrophe and confers tumor suppression.bioRxiv : the preprint server for biology · 2026Article
- NFYA regulates two sequential genome-wide transcriptional activation events during oocyte to embryo transition.bioRxiv : the preprint server for biology · 2026Article
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Molecular mechanisms and consequences of TDP-43 phosphorylation in neurodegeneration.Molecular neurodegeneration · 2025Review
- Role of HSF1 in cell division, tumorigenesis and therapy: a literature review.Cell division · 2025Review
- Hyperbaric oxygen pretreatment on endothelial cell injury via heat shock factor 1 in decompression sickness.Frontiers in molecular biosciences · 2025Article
- Review
- The Role of Heat Shock Factor 1 in Preserving Proteomic Integrity During Copper-Induced Cellular Toxicity.International journal of molecular sciences · 2024Article
- Proteostasis perturbation of N-Myc leveraging HSP70 mediated protein turnover improves treatment of neuroendocrine prostate cancer.Nature communications · 2024Article
- A novel chemical genetic approach reveals paralog-specific role of ERK1/2 in mouse embryonic stem cell fate control.Frontiers in cell and developmental biology · 2024Article
- HSF1 at the crossroads of chemoresistance: from current insights to future horizons in cell death mechanisms.Frontiers in cell and developmental biology · 2024Review
- Modulation of the proteostasis network promotes tumor resistance to oncogenic KRAS inhibitors.Science (New York, N.Y.) · 2023Article
- Heat shock factor 1 (HSF1) specifically potentiates c-MYC-mediated transcription independently of the canonical heat shock response.Cell reports · 2023Article
- Exploiting the intrinsic misfolding propensity of the KRAS oncoprotein.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
36 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
7 authors at 1 institution in 1 country.
Funding
Abstract
Signaling through RAS/MAP kinase pathway is central to biology. ERK has long been perceived as the only substrate for MEK. Here, we report that HSF1, the master regulator of the proteotoxic stress response, is a new MEK substrate. Beyond mediating cell-environment interactions, the MEK-HSF1 regulation impacts malignancy. In tumor cells, MEK blockade inactivates HSF1 and thereby provokes proteomic chaos, presented as protein destabilization, aggregation, and, strikingly, amyloidogenesis. Unlike their non-transformed counterparts, tumor cells are particularly susceptible to proteomic perturbation and amyloid induction. Amyloidogenesis is tumor suppressive, reducing in vivo melanoma growth and contributing to the potent anti-neoplastic effects of proteotoxic stressors. Our findings unveil a key biological function of the oncogenic RAS-MEK signaling in guarding proteostasis and suppressing amyloidogenesis. Thus, proteomic instability is an intrinsic feature of malignant state, and disrupting the fragile tumor proteostasis to promote amyloidogenesis may be a feasible therapeutic strategy.
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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.