ArticleOncotarget2016
Inhibition of endoplasmic reticulum (ER) stress sensors sensitizes cancer stem-like cells to ER stress-mediated apoptosis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- NHE7-Driven endoplasmic reticulum stress signaling transmission promotes malignant progression of endometrial cancer via c-Fos/PRSS1/ERP27 axis.Journal of experimental & clinical cancer research : CR · 2026Article
- Synergistic Molecular Strategies for Targeting the Unfolded Protein Response in Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Non-genetic inactivation of caspase-3 and P53 increases cancer cell fitness by PDIA4 redistribution.Oncogene · 2025Article
- The Role of Endoplasmic Reticulum Stress and Unfolded Protein Response in Gynecological Cancers: A Narrative Review.Cureus · 2025Review
- Glutamate promotes triple-negative breast cancer development through IRE1α/XBP1-mediated macrophage polarization: mechanism insights and therapy.Discover oncology · 2025Article
- Trace elements and metal nanoparticles: mechanistic approaches to mitigating chemotherapy-induced toxicity-a review of literature evidence.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Review
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Identification of microRNA expression profiles of CD44Archives of gynecology and obstetrics · 2022Article
- The inhibition of protein translation promotes tumor angiogenic switch.Molecular biomedicine · 2022Article
- Hypoxia, endoplasmic reticulum stress and chemoresistance: dangerous liaisons.Journal of experimental & clinical cancer research : CR · 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
- Adaptive response of resistant cancer cells to chemotherapy.Cancer biology & medicine · 2020Review
- Lipids in the tumor microenvironment: From cancer progression to treatment.Progress in lipid research · 2020Review
- Dihydroartemisinin-induced unfolded protein response feedback attenuates ferroptosis via PERK/ATF4/HSPA5 pathway in glioma cells.Journal of experimental & clinical cancer research : CR · 2019Article
- Angiotensin II promotes ovarian cancer spheroid formation and metastasis by upregulation of lipid desaturation and suppression of endoplasmic reticulum stress.Journal of experimental & clinical cancer research : CR · 2019Article
- Nuclear factor-kappa B-dependent X-box binding protein 1 signalling promotes the proliferation of nucleus pulposus cells under tumour necrosis factor alpha stimulation.Cell proliferation · 2019Article
- Interferon γ suppresses dentin sialophosphoprotein in oral squamous cell carcinoma cells resulting in antitumor effects, via modulation of the endoplasmic reticulum response.International journal of oncology · 2018Article
- Recombinant Newcastle disease virus expressing human IFN-λ1 (rL-hIFN-λ1)-induced apoptosis of A549 cells is connected to endoplasmic reticulum stress pathways.Thoracic cancer · 2018Article
- Endoplasmic reticulum stress signaling and chemotherapy resistance in solid cancers.Oncogenesis · 2017Review
- Article
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although cancer stem cells (CSC) have been implicated in the development of resistance to anti-cancer therapy including chemotherapy, the mechanisms underlying chemo-resistance by CSC have not yet been elucidated. We herein isolated sphere-forming (cancer stem-like) cells from the cervical cancer cell line, SiHa, and examined the unfolded protein reaction (UPR) to chemotherapeutic-induced endoplasmic reticulum (ER) stress. We revealed that tunicamycin-induced ER stress-mediated apoptosis occurred in monolayer, but not sphere-forming cells. Biochemical assays demonstrated that sphere-forming cells were shifted to pro-survival signaling through the inactivation of IRE1 (XBP-1 splicing) and activation of PERK (elF2α phosphorylation) branches under tunicamycin-induced ER stress conditions. The proportion of apoptotic cells among sphere-forming cells was markedly increased by the tunicamycin+PERK inhibitor (PERKi) treatment, indicating that PERKi sensitized sphere-forming cells to tunicamycin-induced apoptosis. Cisplatin is also known to induce ER stress-mediated apoptosis. A low concentration of cisplatin failed to shift sphere-forming cells to apoptosis, although IRE1 branch, but not PERK, was activated. ER stress-mediated apoptosis occurred in sphere-forming cells by the cisplatin+IRE1α inhibitor (IRE1i) treatment. IRE1i, synergistic with cisplatin, up-regulated elF2α phosphorylation, and this was followed by the induction of CHOP in sphere-forming cells. The results of the present study demonstrated that the inhibition of ER stress sensors, combined with ER stress-inducible chemotherapy, shifted cancer stem-like cells to ER stress-mediated apoptosis.
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Registered trials
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