ArticlePLoS genetics2016
PERK Is a Haploinsufficient Tumor Suppressor: Gene Dose Determines Tumor-Suppressive Versus Tumor Promoting Properties of PERK in Melanoma.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 52 citations in OpenAlex.
- The integrated stress response in cancer: mechanisms of tumor adaptation and therapeutic targeting.Biochemical Society transactions · 2026Review
- ER stress tolerance is regulated by copper-dependent PERK kinase activity.Cell reports · 2025Article
- Endoplasmic reticulum stress responses in anticancer immunity.Nature reviews. Cancer · 2025Review
- Inhibition of the Integrated stress response by Epstein-Barr virus oncoprotein LMP1 attenuates epithelial cell differentiation and lytic viral reactivation.PLoS pathogens · 2025Article
- Fragility of ER homeostatic regulation underlies haploid instability in human somatic cells.The Journal of biological chemistry · 2024Article
- Gene Expression Profiling to Unfolded Proteins Response as a Risk Modulator of Patients with Rheumatoid Arthritis.International journal of molecular sciences · 2024Article
- Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy.Cell communication and signaling : CCS · 2024Review
- Performance of Green Desymmetrization Methods toward Bioactive Cephalostatin Analogues.Current medicinal chemistry · 2024Review
- PERK Inhibition by HC-5404 Sensitizes Renal Cell Carcinoma Tumor Models to Antiangiogenic Tyrosine Kinase Inhibitors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- UPR-Induced miR-616 Inhibits Human Breast Cancer Cell Growth and Migration by Targeting c-MYC.International journal of molecular sciences · 2023Article
- Induction of the activating transcription factor-4 in the intratumoral CD8+ T cells sustains their viability and anti-tumor activities.Cancer immunology, immunotherapy : CII · 2023Article
- Major roles of the circadian clock in cancer.Cancer biology & medicine · 2023Review
- The integrated stress response in cancer progression: a force for plasticity and resistance.Frontiers in oncology · 2023Review
- SEL1L-HRD1 ER-associated degradation suppresses hepatocyte hyperproliferation and liver cancer.iScience · 2022Article
- Review
- ER residential chaperone GRP78 unconventionally relocalizes to the cell surface via endosomal transport.Cellular and molecular life sciences : CMLS · 2021Article
- Endoplasmic reticulum stress signals in the tumour and its microenvironment.Nature reviews. Cancer · 2021Review
- Structural and Functional Significance of the Endoplasmic Reticulum Unfolded Protein Response Transducers and Chaperones at the Mitochondria-ER Contacts: A Cancer Perspective.Frontiers in cell and developmental biology · 2021Review
- Proteotoxic Stress and Cell Death in Cancer Cells.Cancers · 2020Review
- Endoplasmic Reticulum Stress Signaling in Cancer Cells.The American journal of pathology · 2020Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
The unfolded protein response (UPR) regulates cell fate following exposure of cells to endoplasmic reticulum stresses. PERK, a UPR protein kinase, regulates protein synthesis and while linked with cell survival, exhibits activities associated with both tumor progression and tumor suppression. For example, while cells lacking PERK are sensitive to UPR-dependent cell death, acute activation of PERK triggers both apoptosis and cell cycle arrest, which would be expected to contribute tumor suppressive activity. We have evaluated these activities in the BRAF-dependent melanoma and provide evidence revealing a complex role for PERK in melanoma where a 50% reduction is permissive for BrafV600E-dependent transformation, while complete inhibition is tumor suppressive. Consistently, PERK mutants identified in human melanoma are hypomorphic with dominant inhibitory function. Strikingly, we demonstrate that small molecule PERK inhibitors exhibit single agent efficacy against BrafV600E-dependent tumors highlighting the clinical value of targeting PERK.
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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.