ArticleNeuro-oncology2020
GRP94 promotes brain metastasis by engaging pro-survival autophagy.
Article in Neuro-oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Molecular and Clinicopathological Biomarkers Predicting Brain Metastasis in Triple-Negative Breast Cancer: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Acoustoelectric nanoregulator for modulating the endoplasmic reticulum and mitochondria in cell fate regulation.Bioactive materials · 2027Article
- Decoding autophagy in neuro-tumor crosstalk: from underlying mechanisms to translational opportunities.Theranostics · 2026Review
- Breast cancer brain metastasis: from molecular insights to therapeutic innovation.Frontiers in immunology · 2026Review
- ATM interaction with GRP94 modulates oncogenic receptor expression and signaling and microglial activation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Endosome-phagophore linking assemblies for the degradation of membrane/extracellular proteins.Nature communications · 2025Article
- Beyond Folding: Expanding the Functional Landscape of Hsp90 Chaperone Machinery in Health and Disease.International journal of molecular sciences · 2025Review
- Endoplasmic reticulum stress signaling modulates ischemia/reperfusion injury in the aged heart by regulating mitochondrial maintenance.Molecular medicine (Cambridge, Mass.) · 2024Review
- CK2α-mediated phosphorylation of GRP94 facilitates the metastatic cascade in triple-negative breast cancer.Cell death discovery · 2024Article
- Radioresistance and brain metastases: a review of the literature and applied perspective.Frontiers in oncology · 2024Review
- Mechanisms of Organ-Specific Metastasis of Breast Cancer.Cold Spring Harbor perspectives in medicine · 2023Review
- The Role of Autophagy in Breast Cancer Metastasis.Biomedicines · 2023Review
- The biology and inhibition of glucose-regulated protein 94/gp96.Medicinal research reviews · 2022Review
- Repurposing autophagy regulators in brain tumors.International journal of cancer · 2022Review
- Biomimetic Lipopolysaccharide-Free Bacterial Outer Membrane-Functionalized Nanoparticles for Brain-Targeted Drug Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- In Silico Evaluation of Natural Compounds for an Acidic Extracellular Environment in Human Breast Cancer.Cells · 2021Article
- Breast cancer brain metastasis: insight into molecular mechanisms and therapeutic strategies.British journal of cancer · 2021Review
- Molecular Chaperone GRP94/GP96 in Cancers: Oncogenesis and Therapeutic Target.Frontiers in oncology · 2021Review
- Autophagy-mediated tumor cell survival and progression of breast cancer metastasis to the brain.Journal of Cancer · 2021Review
- Comment on "GRP94 promotes brain metastasis by engaging pro-survival autophagy".Neuro-oncology · 2020Article
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14 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGRP94 is a glucose-regulated protein critical for survival in endoplasmic reticulum stress. Expression of GRP94 is associated with cellular transformation and increased tumorigenicity in breast cancer. Specifically, overexpression of GRP94 predicts brain metastasis (BM) in breast carcinoma patients with either triple negative or ErbB2 positive tumors. The aim of this study was to understand if microenvironmental regulation of GRP94 expression might be a hinge orchestrating BM progression.
methodsGRP94 ablation was performed in a BM model BR-eGFP-CMV/Luc-V5CA1 (BRV5CA1) of breast cancer. In vitro results were validated in a dataset of 29 metastases in diverse organs from human breast carcinomas and in BM tissue from tumors of different primary origin. BM patient-derived xenografts (PDXs) were used to test sensitivity to the therapeutic approach.
resultsBMs that overexpress GRP94 as well as tumor necrosis factor receptor-associated factor 2 are more resistant to glucose deprivation by induction of anti-apoptotic proteins (B-cell lymphoma 2 and inhibitors of apoptosis proteins) and engagement of pro-survival autophagy. GRP94 ablation downregulated autophagy in tumor cells, resulting in increased BM survival in vivo. These results were validated in a metastasis dataset from human patients, suggesting that targeting autophagy might be strategic for BM prevention. Indeed, hydroxychloroquine treatment of preclinical models of BM from PDX exerts preventive inhibition of tumor growth (P < 0.001).
conclusionsWe show that GRP94 is directly implicated in BM establishment by activating pro-survival autophagy. Disruption of this compensatory fueling route might prevent metastatic growth.
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