ArticleNature cell biology2020
ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism.
Article in Nature cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers, 1 of them a synthesis that pooled it.
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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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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
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- What is the Impact of Endothelial-to-Mesenchymal Transition in Solid Tumours: A Qualitative Systematic Review and Quantitative Meta-Analysis.International journal of biological sciences · 2025Pooled it
- Integrative omics profiling of CRELD2 in ccRCC: a nexus of genetics, prognosis, and tumor microenvironment.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Single-nuclei UPR profiling by flow cytometry reveals bortezomib resistance mechanisms in multiple myeloma.EMBO molecular medicine · 2026Article
- Transformative biomechanics and mechanobiology breakthroughs shaping the future of health and medicine.Innovation (Cambridge (Mass.)) · 2026Review
- Compressive stress-driven Piezo1 activation and Rho-ROCK mechanotransduction promote tumor progression via epigenetic mechanical memory.Science advances · 2026Article
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Endothelial cell-secreted bone targeting exosomes promote angiogenesis coupling with osteogenesis via the PERK-ATF4-CRELD2 pathway.Stem cell research & therapy · 2025Article
- A preliminary study on the prognostic significance of cysteine-rich EGF ligand domain 2 protein (CRELD2) in patients with triple negative breast cancer.Biomolecules & biomedicine · 2025Article
- Endoplasmic reticulum stress-induced CRELD2 promotes APMAP-mediated activation of TGF-β/SMAD and NF-κB pathways in esophageal squamous cell carcinoma.Frontiers in immunology · 2025Article
- Enhanced RHO-ROCK signaling is associated with CRELD2 production and fibroblast recruitment in cutaneous squamous cell carcinoma.Cytoskeleton (Hoboken, N.J.) · 2024Article
- CAF-Associated Genes in Breast Cancer for Novel Therapeutic Strategies.Biomedicines · 2024Review
- MOTAI: A Novel Method for the Study of O-GalNAcylation and Complex O-Glycosylation in Cancer.Analytical chemistry · 2024Article
- Molecular characterization of the ER stress-inducible factor CRELD2.Cell biochemistry and biophysics · 2024Article
- Tumor Biomechanics Alters Metastatic Dissemination of Triple Negative Breast Cancer via Rewiring Fatty Acid Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Integrative analysis with machine learning identifies diagnostic and prognostic signatures in neuroblastoma based on differentially DNA methylated enhancers between INSS stage 4 and 4S neuroblastoma.Journal of cancer research and clinical oncology · 2024Article
- Cysteine-rich with EGF-like domains 2 (CRELD2) is an endoplasmic reticulum stress-inducible angiogenic growth factor promoting ischemic heart repair.Nature cardiovascular research · 2024Article
- The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy.Frontiers in immunology · 2024Review
- Molecular signature of stem-like glioma cells (SLGCs) from human glioblastoma and gliosarcoma.PloS one · 2024Article
- Unveiling the role of osteosarcoma-derived secretome in premetastatic lung remodelling.Journal of experimental & clinical cancer research : CR · 2023Article
- Fasudil promotes polyploidization of megakaryoblasts in an acute megakaryocyte leukemia model.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is well accepted that cancers co-opt the microenvironment for their growth. However, the molecular mechanisms that underlie cancer-microenvironment interactions are still poorly defined. Here, we show that Rho-associated kinase (ROCK) in the mammary tumour epithelium selectively actuates protein-kinase-R-like endoplasmic reticulum kinase (PERK), causing the recruitment and persistent education of tumour-promoting cancer-associated fibroblasts (CAFs), which are part of the cancer microenvironment. An analysis of tumours from patients and mice reveals that cysteine-rich with EGF-like domains 2 (CRELD2) is the paracrine factor that underlies PERK-mediated CAF education downstream of ROCK. We find that CRELD2 is regulated by PERK-regulated ATF4, and depleting CRELD2 suppressed tumour progression, demonstrating that the paracrine ROCK-PERK-ATF4-CRELD2 axis promotes the progression of breast cancer, with implications for cancer therapy.
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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.