ArticleMolecular cancer2017
PERK induces resistance to cell death elicited by endoplasmic reticulum stress and chemotherapy.
Article in Molecular cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.
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Who cites it
123 citing papers in PubMed, 204 citations in OpenAlex.
- Unfolded Protein Response Pathways in Cancer: Mechanisms, Tumor Biology and Therapeutic Opportunities.Molecular diagnosis & therapy · 2026Review
- CaMaterials today. Bio · 2026Article
- Nanoplatforms for EGFR-TKI resistance reversion and immunoactivation in NSCLC by ER stress and siRNA intervention.Journal of nanobiotechnology · 2026Article
- Simvastatin reprograms lipid metabolism in B16.F10 melanoma cells to favor an early resistant phenotype.Scientific reports · 2026Article
- Integration of 117 machine learning algorithms and single-cell transcriptomics identifies macrophage polarization and ER stress signatures for cancer prognosis and precision therapy.Discover oncology · 2026Article
- Pan-cancer analysis reveals differential PERK expression across tumour types and its potential as a therapeutic target.Discover oncology · 2026Article
- Noncanonical role of KDM5C in conferring bortezomib resistance via the PERK‒Nrf2 axis in multiple myeloma.Cell death & disease · 2026Article
- ASCC3 promotes chemosensitivity in colorectal cancer cells.Scientific reports · 2026Article
- Ferroptosis as a Novel Therapeutic Strategy to Overcome Multidrug Resistance in Colorectal Cancer.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Article
- BRCA1 alleviates inflammation, oxidative stress, and ovarian granulosa cell apoptosis by inhibiting endoplasmic reticulum stress, thereby ameliorating polycystic ovary syndrome.European journal of medical research · 2026Article
- Targeting the unfolded protein response in cancer: mechanisms, small-molecule inhibitors, and translational challenges.Frontiers in immunology · 2026Review
- Optimization extraction of Allium mongolicum Regel polysaccharide and alleviation of intestinal injury via inhibition of the PERK/ATF4/CHOP signaling pathway.Frontiers in veterinary science · 2026Article
- BCAM-AKT2 fusion protein promotes unfolded protein response driven oncogenic signaling in SKOV3 epithelial ovarian cancer cell line.PloS one · 2026Article
- Cancer Cell Dormancy and Chemotherapy Resistance.Journal of Cancer · 2026Review
- USP8 inhibits cigarette smoke extract combined with LPS-induced inflammatory response and ER stress by regulating the ABCB1-mediated MAPK signaling pathway in human bronchial epithelial cells.Journal of inflammation (London, England) · 2025Article
- Unfolded protein response kinase PERK supports survival and metastasis of circulating tumor cell clusters via SAM synthesis and H3K4me3-dependent PDGFB signaling.Cancer communications (London, England) · 2025Article
- Oligoclonal tumor-specific CD8 T-cell revival and IRE1α/XBP1-GDF15-mediated immunosuppressive niches determine neoadjuvant chemoimmunotherapy efficacy in cervical cancer.Journal for immunotherapy of cancer · 2025Article
- Review
- DCF-resistant ESCC redevelops drug sensitivity when combined with calcium channel blockers due to ER stress response.Esophagus : official journal of the Japan Esophageal Society · 2025Article
63 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNutrient deprivation, hypoxia, radiotherapy and chemotherapy induce endoplasmic reticulum (ER) stress, which activates the so-called unfolded protein response (UPR). Extensive and acute ER stress directs the UPR towards activation of death-triggering pathways. Cancer cells are selected to resist mild and prolonged ER stress by activating pro-survival UPR. We recently found that drug-resistant tumor cells are simultaneously resistant to ER stress-triggered cell death. It is not known if cancer cells adapted to ER stressing conditions acquire a chemoresistant phenotype.
methodsTo investigate this issue, we generated human cancer cells clones with acquired resistance to ER stress from ER stress-sensitive and chemosensitive cells.
resultsER stress-resistant cells were cross-resistant to multiple chemotherapeutic drugs: such multidrug resistance (MDR) was due to the overexpression of the plasma-membrane transporter MDR related protein 1 (MRP1). Gene profiling analysis unveiled that cells with acquired resistance to ER stress and chemotherapy share higher expression of the UPR sensor protein kinase RNA-like endoplasmic reticulum kinase (PERK), which mediated the erythroid-derived 2-like 2 (Nrf2)-driven transcription of MRP1. Disrupting PERK/Nrf2 axis reversed at the same time resistance to ER stress and chemotherapy. The inducible silencing of PERK reduced tumor growth and restored chemosensitivity in resistant tumor xenografts.
conclusionsOur work demonstrates for the first time that the adaptation to ER stress in cancer cells produces a MDR phenotype. The PERK/Nrf2/MRP1 axis is responsible for the resistance to ER stress and chemotherapy, and may represent a good therapeutic target in aggressive and resistant tumors.
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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.