ArticleCancer research2008
Dual function of pancreatic endoplasmic reticulum kinase in tumor cell growth arrest and survival.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 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
67 citing papers in PubMed, 112 citations in OpenAlex.
- Organelle contact sites in cancer cells.Cell death & disease · 2026Review
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- Cancer Cell Dormancy in the Bone Microenvironment.Current osteoporosis reports · 2025Review
- Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma.Clinical and experimental medicine · 2025Review
- The PERK/ATF4 pathway is required for metabolic reprogramming and progressive lung fibrosis.JCI insight · 2025Article
- Endoplasmic Reticulum Stress in Cancer Progression: A Comprehensive Review of Its Role and Mechanisms.International journal of medical sciences · 2025Review
- Stress response regulation of mRNA translation: Implications for antioxidant enzyme expression in cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Review
- How much do we know about the metastatic process?Clinical & experimental metastasis · 2024Review
- Activation of the PERK/eIF2α axis is a pivotal prerequisite of taxanes to cancer cell apoptosis and renders synergism to overcome paclitaxel resistance in breast cancer cells.Cancer cell international · 2024Article
- mTOR pathway occupies a central role in the emergence of latent cancer cells.Cell death & disease · 2024Review
- A PERK-Specific Inhibitor Blocks Metastatic Progression by Limiting Integrated Stress Response-Dependent Survival of Quiescent Cancer Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Article
- Unfolded protein response and angiogenesis in malignancies.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Autophagy, molecular chaperones, and unfolded protein response as promoters of tumor recurrence.Cancer metastasis reviews · 2023Review
- Intratumoral microbiota: roles in cancer initiation, development and therapeutic efficacy.Signal transduction and targeted therapy · 2023Review
- Role of symmetry in 3,3-diphenyl-1,3-dihydroindol-2-one derivatives as inhibitors of translation initiation.Bioorganic & medicinal chemistry letters · 2023Article
- Immunogenic landscape and risk score prediction based on unfolded protein response (UPR)-related molecular subtypes in hepatocellular carcinoma.Frontiers in immunology · 2023Article
- C4orf47 contributes to the dormancy of pancreatic cancer under hypoxic conditions.Journal of Cancer · 2023Article
- The endoplasmic reticulum stress response in prostate cancer.Nature reviews. Urology · 2022Review
- Ablation of the endoplasmic reticulum stress kinase PERK induces paraptosis and type I interferon to promote anti-tumor T cell responses.Cancer cell · 2022Article
7 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
5 authors at 1 institution in 1 country.
Funding
Abstract
Pancreatic endoplasmic reticulum kinase (PERK)-eIF2 alpha signaling, a component of the endoplasmic reticulum (ER) stress response, has been proposed as a therapeutic target due to its importance to cell survival in hypoxic tumors. In this study, we show that in addition to promoting survival, PERK can also suppress tumor growth of advanced carcinomas. Our results show that in squamous carcinoma T-HEp3 cells, which display low PERK-eIF2 alpha signaling, inducible activation of an Fv2E-PERK fusion protein results in a strong G(0)-G(1) arrest in vitro. Most importantly, Fv2E-PERK activation, in addition to promoting survival in vitro, inhibits T-HEp3 and SW620 colon carcinoma growth in vivo. Increased PERK activation is linked to enhanced p-eIF2 alpha levels, translational repression, and a decrease in Ki67, pH 3, and cycD1/D3 levels, but not to changes in angiogenesis or apoptosis. Experimental reduction of PERK activity, or overexpression of GADD34 in a spontaneously arising in vivo quiescent variant of HEp3 cells that displays strong basal PERK-eIF2 alpha activation, reverts their quiescent phenotype. We conclude that the growth-inhibitory function of PERK is preserved in tumors and upon proper reactivation can severely inhibit tumor growth through induction of quiescence. This is an important consideration in the development of PERK-based therapies, as its inhibition may facilitate the proliferation of slow-cycling or dormant tumor cells.
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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.