ArticleMolecular and cellular biology2006
Perk-dependent translational regulation promotes tumor cell adaptation and angiogenesis in response to hypoxic stress.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 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.
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Who cites it
160 citing papers in PubMed, 287 citations in OpenAlex.
- Rho GTPase-driven stress granules enable anchorage-independent survival under adhesion stress.Research square · 2026Article
- Deciphering the interplay between hypoxia, angiogenesis, and endoplasmic reticulum stress in carcinogenesis: A narrative review.World journal of experimental medicine · 2026Review
- Review
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- ER Stress Is Associated with a "Mesenchymal Drift" in an Anaplastic Thyroid Carcinoma Cell Line.Cancers · 2025Article
- ER stress tolerance is regulated by copper-dependent PERK kinase activity.Cell reports · 2025Article
- The role of the unfolded protein response pathway in bone homeostasis and potential therapeutic target in cancer-associated bone disease.Bone research · 2025Review
- PERK-Olating Through Cancer: A Brew of Cellular Decisions.Biomolecules · 2025Review
- Adaptation of Natural Killer Cells to Hypoxia: A Review of the Transcriptional, Translational, and Metabolic Processes.ImmunoTargets and therapy · 2025Review
- Exploring the dual role of endoplasmic reticulum stress in urological cancers: Implications for tumor progression and cell death interactions.Journal of cell communication and signaling · 2024Review
- Protein-rich foods, sea foods, and gut microbiota amplify immune responses in chronic diseases and cancers - Targeting PERK as a novel therapeutic strategy for chronic inflammatory diseases, neurodegenerative disorders, and cancer.Pharmacology & therapeutics · 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
- How the Unfolded Protein Response Is a Boon for Tumors and a Bane for the Immune System.ImmunoHorizons · 2023Review
- The unfolded protein response (UPR) pathway: the unsung hero in breast cancer management.Apoptosis : an international journal on programmed cell death · 2023Review
- The integrated stress response in cancer progression: a force for plasticity and resistance.Frontiers in oncology · 2023Review
- The endoplasmic reticulum stress response in prostate cancer.Nature reviews. Urology · 2022Review
- Review
- Protein synthesis control in cancer: selectivity and therapeutic targeting.The EMBO journal · 2022Review
- The Regulation of Endoplasmic Reticulum Stress in Cancer: Special Focuses on Luteolin Patents.Molecules (Basel, Switzerland) · 2022Review
- Adaptive and maladaptive roles of lipid droplets in health and disease.American journal of physiology. Cell physiology · 2022Review
100 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
11 authors at 5 institutions in 2 countries.
Funding
Abstract
It has been well established that the tumor microenvironment can promote tumor cell adaptation and survival. However, the mechanisms that influence malignant progression have not been clearly elucidated. We have previously demonstrated that cells cultured under hypoxic/anoxic conditions and transformed cells in hypoxic areas of tumors activate a translational control program known as the integrated stress response (ISR). Here, we show that tumors derived from K-Ras-transformed Perk(-/-) mouse embryonic fibroblasts (MEFs) are smaller and exhibit less angiogenesis than tumors with an intact ISR. Furthermore, Perk promotes a tumor microenvironment that favors the formation of functional microvessels. These observations were corroborated by a microarray analysis of polysome-bound RNA in aerobic and hypoxic Perk(+/+) and Perk(-/-) MEFs. This analysis revealed that a subset of proangiogenic transcripts is preferentially translated in a Perk-dependent manner; these transcripts include VCIP, an adhesion molecule that promotes cellular adhesion, integrin binding, and capillary morphogenesis. Taken with the concomitant Perk-dependent translational induction of additional proangiogenic genes identified by our microarray analysis, this study suggests that Perk plays a role in tumor cell adaptation to hypoxic stress by regulating the translation of angiogenic factors necessary for the development of functional microvessels and further supports the contention that the Perk pathway could be an attractive target for novel antitumor modalities.
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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.