ArticleThe Journal of biological chemistry2011
Novel mechanism of anti-apoptotic function of 78-kDa glucose-regulated protein (GRP78): endocrine resistance factor in breast cancer, through release of B-cell lymphoma 2 (BCL-2) from BCL-2-interacting killer (BIK).
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 124 citations in OpenAlex.
- Article
- Article
- The role of UPR-related long noncoding RNAs in development of endocrine resistance in breast cancer.International journal of cancer · 2025Review
- A new era in cancer therapy: targeting the Proteasome-Bcl-2 axis.Journal of experimental & clinical cancer research : CR · 2025Review
- Cancer-Targeting Peptides Functionalized With Polyarginine Enables GRP78-Dependent Cell Uptake and siRNA Delivery Within the DU145 Prostate Cancer Cells.Journal of peptide science : an official publication of the European Peptide Society · 2025Article
- GRP78 as a potential therapeutic target in cancer treatment: an updated review of its role in chemoradiotherapy resistance of cancer cells.Medical oncology (Northwood, London, England) · 2025Review
- The Landscape of Potential Targeted Treatments and Chemotherapy Efficacy Biomarkers for TNBC.Breast cancer (Dove Medical Press) · 2025Review
- Deoxypodophyllotoxin Mediates Autophagy Death through Inhibition of GRP78 in Human Osteosarcoma.Current cancer drug targets · 2025Article
- Pharmacological Features and Therapeutic Implications of Plumbagin in Cancer and Metabolic Disorders: A Narrative Review.Nutrients · 2024Review
- Targeting PAK4 reverses cisplatin resistance in NSCLC by modulating ER stress.Cell death discovery · 2024Article
- Introduction of a new recombinant vaccine based on GRP78 for breast cancer immunotherapy and evaluation in a mouse model.BioImpacts : BI · 2024Article
- The unfolded protein response (UPR) pathway: the unsung hero in breast cancer management.Apoptosis : an international journal on programmed cell death · 2023Review
- Article
- Down-regulating GRP78 reverses pirarubicin resistance of triple negative breast cancer by miR-495-3p mimics and involves the p-AKT/mTOR pathway.Bioscience reports · 2022Article
- Regulation of Bcl-2 Family Proteins in Estrogen Receptor-Positive Breast Cancer and Their Implications in Endocrine Therapy.Cancers · 2022Review
- Proteomic Research on the Antitumor Properties of Medicinal Mushrooms.Molecules (Basel, Switzerland) · 2021Review
- Review
- Altered glycolysis results in drug-resistant in clinical tumor therapy.Oncology letters · 2021Review
- The role of MET in chemotherapy resistance.Oncogene · 2021Review
- Mining prognostic markers of Asian hepatocellular carcinoma patients based on the apoptosis-related genes.BMC cancer · 2021Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Activation of the intrinsic apoptotic pathway represents a major mechanism for breast cancer regression resulting from anti-estrogen therapy. The BH3-only protein BIK is inducible by estrogen-starvation and anti-estrogen treatment and plays an important role in anti-estrogen induced apoptosis of breast cancer cells. BIK is predominantly localized to the endoplasmic reticulum where it regulates BAX/BAK-dependent release of Ca(2+) from the endoplasmic reticulum stores and cooperates with other BH3-only proteins such as NOXA to cause rapid release of cytochrome c from mitochondria and activate apoptosis. BIK is also known to inactivate BCL-2 through complex formation. Previously, we demonstrated that apoptosis triggered by BIK in estrogen-starved human breast cancer cells is suppressed by GRP78, a major endoplasmic reticulum chaperone. Here we described the isolation of a novel clonal human breast cancer cell line (MCF-7/BUS-10) resistant to long-term estrogen deprivation. These cells exhibit elevated level of GRP78, which protects them from estrogen starvation-induced apoptosis. Our studies revealed that overexpression of GRP78 suppresses apoptosis induced by BIK and NOXA, either alone or in combination. Surprisingly, the interaction of GRP78 with BIK does not require its BH3 domain, which has been implicated in all previous BIK protein interactions. We further showed GRP78 and BCL-2 form independent complex with BIK and that increased expression of GRP78 decreases BIK binding to BCL-2. Our findings provide the first evidence that GRP78 can decrease BCL-2 sequestration by BIK at the endoplasmic reticulum, thus uncovering a potential new mechanism whereby GRP78 confers endocrine resistance in breast cancer.
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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.