ArticlePloS one2014
Glucose-regulated protein 78 (Grp78) confers chemoresistance to tumor endothelial cells under acidic stress.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Effects of extracellular acidity on resistance to chemotherapy treatment: a systematic review.Medical oncology (Northwood, London, England) · 2018Pooled it
- GRP78 Promotes Neural Stem Cell Antiapoptosis and Survival in Response to Oxygen-Glucose Deprivation (OGD)/Reoxygenation through PI3K/Akt, ERK1/2, and NF-Oxidative medicine and cellular longevity · 2018Guideline
- Methylation heterogeneity of the AQP1 promoter as a candidate prognostic biomarker in cholangiocarcinoma.Scientific reports · 2026Article
- Resistance to neoadjuvant chemotherapy in breast cancers: a metabolic perspective.Journal of experimental & clinical cancer research : CR · 2025Review
- GRP78 Nanobody-Directed Immunotoxin Activates Innate Immunity Through STING Pathway to Synergize Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Overexpression ofOncology letters · 2025Article
- Parahydrogen-enhanced pH measurements using [1-The Analyst · 2024Article
- Nitric oxide has diverse effects on head and neck cancer cell proliferation and glycolysis.Biomedical reports · 2024Article
- Review
- COVID-19-Associated Rhinocerebral Mucormycosis, an Incidental Finding or a Matter of Concern - Mixed-Method Systematic Review.Infection and drug resistance · 2024Review
- Recent development of pH-responsive theranostic nanoplatforms for magnetic resonance imaging-guided cancer therapy.Exploration (Beijing, China) · 2023Review
- Potential to Eradicate Cancer Stemness by Targeting Cell Surface GRP78.Biomolecules · 2022Review
- The Pathogenetic Dilemma of Post-COVID-19 Mucormycosis in India.Aging and disease · 2022Article
- The Mechanism of Warburg Effect-Induced Chemoresistance in Cancer.Frontiers in oncology · 2021Review
- Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency.International journal of molecular sciences · 2020Article
- GRP78 targeting: Hitting two birds with a stone.Life sciences · 2020Review
- Activation of pH-Sensing Receptor OGR1 (GPR68) Induces ER Stress Via the IRE1α/JNK Pathway in an Intestinal Epithelial Cell Model.Scientific reports · 2020Article
- Using Serological Proteome Analysis to Identify and Evaluate Anti-GRP78 Autoantibody as Biomarker in the Detection of Gastric Cancer.Journal of oncology · 2020Article
- Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1.Cancer science · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesThis study was designed to investigate the activation of the unfolded protein response (UPR) in tumor associated endothelial cells (TECs) and its association with chemoresistance during acidic pH stress. MATERIALS AND
methodsEndothelial cells from human oral squamous cell carcinomas (OSCC) were excised by laser capture microdissection (LCM) followed by analysis of UPR markers (Grp78, ATF4 and CHOP) using quantitative PCR. Grp78 expression was also determined by immunostaining. Acidic stress was induced in primary human dermal microvascular endothelial cells (HDMECs) by treatment with conditioned medium (CM) from tumor cells grown under hypoxic conditions or by adjusting medium pH to 6.4 or 7.0 using lactic acid or hydrochloric acid (HCl). HDMEC resistance to the anti-angiogenic drug Sunitinib was assessed with SRB assay.
resultsUPR markers, Grp78, ATF4 and CHOP were significantly upregulated in TECs from OSCC compared to HDMECs. HDMECs cultured in acidic CM (pH 6.0-6.4) showed increased expression of the UPR markers. However, severe acidosis led to marked cell death in HDMECs. Alternatively, HDMECs were able to adapt when exposed to chronic acidosis at pH 7.0 for 7 days, with concomittant increase in Grp78 expression. Chronic acidosis also confers drug resistance to HDMECs against Sunitinib. Knockdown of Grp78 using shRNA resensitizes HDMECs to drug treatment.
conclusionsUPR induction in ECs under acidic pH conditions is related to chemoresistance and may contribute to therapeutic failures in response to chemotherapy. Targeting Grp78, the key component of the UPR pathway, may provide a promising approach to overcome ECs resistance in cancer therapy.
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