ArticleCell death & disease2014
A gain-of-function mutant p53-HSF1 feed forward circuit governs adaptation of cancer cells to proteotoxic stress.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 111 citations in OpenAlex.
- Trial
- Article
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Protein kinase CK2 sustains de novo fatty acid synthesis by regulating the expression of SCD-1 in human renal cancer cells.Cancer cell international · 2024Article
- Review
- Visualization of Brain Tumors with Infrared-Labeled Aptamers for Fluorescence-Guided Surgery.Journal of the American Chemical Society · 2024Article
- Recent Advances on Mutant p53: Unveiling Novel Oncogenic Roles, Degradation Pathways, and Therapeutic Interventions.Biomolecules · 2024Review
- BMP Stimulation Differentially Affects Phosphorylation and Protein Stability of β-Catenin in Breast Cancer Cell Lines.International journal of molecular sciences · 2024Article
- HSF1 and Its Role in Huntington's Disease Pathology.Advances in experimental medicine and biology · 2023Review
- Proteasome regulators in pancreatic cancer.World journal of gastrointestinal oncology · 2022Review
- Suppression of HSF1 activity by wildtype p53 creates a driving force for p53 loss-of-heterozygosity.Nature communications · 2021Article
- Review
- Thrombospondin 4/integrin α2/HSF1 axis promotes proliferation and cancer stem-like traits of gallbladder cancer by enhancing reciprocal crosstalk between cancer-associated fibroblasts and tumor cells.Journal of experimental & clinical cancer research : CR · 2021Article
- Pan-Cancer Analysis of the Prognostic and Immunological Role of HSF1: A Potential Target for Survival and Immunotherapy.Oxidative medicine and cellular longevity · 2021Article
- The ABL2 kinase regulates an HSF1-dependent transcriptional program required for lung adenocarcinoma brain metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- Gain-of-function mutant p53 in cancer progression and therapy.Journal of molecular cell biology · 2020Review
- Apigenin as Tumor Suppressor in Cancers: Biotherapeutic Activity, Nanodelivery, and Mechanisms With Emphasis on Pancreatic Cancer.Frontiers in chemistry · 2020Review
- Cancer Stemness: p53 at the Wheel.Frontiers in oncology · 2020Review
- STAT3 and mutp53 Engage a Positive Feedback Loop Involving HSP90 and the Mevalonate Pathway.Frontiers in oncology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To overcome proteotoxic stress inherent to malignant transformation, cancer cells induce a range of adaptive mechanisms, with the master transcription factor heat-shock factor 1 (HSF1)-orchestrated response taking center stage. Here we define a novel gain-of-function of mutant p53 (mutp53), whereby mutp53-overexpressing cancer cells acquire superior tolerance to proteotoxic stress. mutp53 via constitutive stimulation of EGFR and ErbB2 signaling hyperactivates the MAPK and PI3K cascades, which induce stabilization and phosphoactivation of HSF1 on Ser326. Moreover, mutp53 protein via direct interaction with activated p-Ser326 HSF1 facilitates HSF1 recruitment to its specific DNA-binding elements and stimulates transcription of heat-shock proteins including Hsp90. In turn, induced Hsp90 stabilizes its oncogenic clients including EGFR, ErbB2 and mutp53, thereby further reinforcing oncogenic signaling. Thus, mutp53 initiates a feed forward loop that renders cancer cells more resistant to adverse conditions, providing a strong survival advantage.
Indexed as
Identifiers
What OpenQuestion holds
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.