ArticleOncogene2015
GPNMB cooperates with neuropilin-1 to promote mammary tumor growth and engages integrin α5β1 for efficient breast cancer metastasis.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- Glycoprotein nonmetastatic melanoma protein b immunohistochemistry can be a useful ancillary tool to diagnose subependymal giant cell astrocytoma.Virchows Archiv : an international journal of pathology · 2025Article
- GPNMB is a novel binding partner of FGFR1 that affects tumorigenic potential through AKT phosphorylation in TNBC.Cancer science · 2025Article
- Integrin β1 in breast cancer: mechanisms of progression and therapy.Breast cancer (Tokyo, Japan) · 2025Review
- The janus-faced biology of GPNMB: from tissue homeostasis to cancer pathogenesis.Frontiers in molecular biosciences · 2025Review
- Management of translocation carcinomas of the kidney.Translational cancer research · 2024Review
- Identification of GPNMB in endometrial cancer based on pan-cancer analysis and in vitro validation.Discover oncology · 2024Article
- Glycoprotein non-metastatic melanoma protein B promotes tumor growth and is a biomarker for lymphangioleiomyomatosis.Endocrine-related cancer · 2024Article
- QSOX2 Upregulated in triple-negative breast cancer exacerbates patient prognosis by stabilizing integrin β1.Heliyon · 2024Article
- The Nervous System Development Regulator Neuropilin-1 as a Potential Prognostic Marker and Therapeutic Target in Brain Cancer.Cancers · 2023Review
- Human Antibody VMolecular pharmaceutics · 2023Article
- Neuropilin-1 Knockout and Rescue Confirms Its Role to Promote Metastasis in MDA-MB-231 Breast Cancer Cells.International journal of molecular sciences · 2023Article
- Downregulation of glycoprotein non-metastatic melanoma protein B prevents high glucose-induced angiogenesis in diabetic retinopathy.Molecular and cellular biochemistry · 2023Article
- Functional role of MicroRNA/PI3K/AKT axis in osteosarcoma.Frontiers in oncology · 2023Review
- GPNMB: a potent inducer of immunosuppression in cancer.Oncogene · 2022Review
- Linkers: An Assurance for Controlled Delivery of Antibody-Drug Conjugate.Pharmaceutics · 2022Review
- Prognostic Value of GPNMB, EGFR, p-PI3K, and Ki-67 in Patients with Esophageal Squamous Cell Carcinoma.Analytical cellular pathology (Amsterdam) · 2022Article
- GPNMB Extracellular Fragment Protects Melanocytes from Oxidative Stress by Inhibiting AKT Phosphorylation Independent of CD44.International journal of molecular sciences · 2021Article
- Anti-inflammatory role of Gpnmb in adipose tissue of mice.Scientific reports · 2021Article
- Expression pattern and prognostic impact of glycoprotein non-metastatic B (GPNMB) in triple-negative breast cancer.Scientific reports · 2021Article
- Immunotherapy for Breast Cancer Treatment.Iranian biomedical journal · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Glycoprotein nmb (GPNMB) promotes breast tumor growth and metastasis and its expression in tumor epithelium correlates with poor prognosis in breast cancer patients. Despite its biological and clinical significance, little is known regarding the molecular mechanisms engaged by GPNMB. Herein, we show that GPNMB engages distinct functional domains and mechanisms to promote primary tumor growth and metastasis. We demonstrate that neuropilin-1 (NRP-1) expression is increased in breast cancer cells that overexpress GPNMB. Interestingly, the GPNMB-driven increase in NRP-1 expression potentiated vascular endothelial growth factor signaling in breast cancer cells and was required for the growth, but not metastasis, of these cells in vivo. Interrogation of RNAseq data sets revealed a positive correlation between GPNMB and NRP-1 levels in human breast tumors. Furthermore, we ascribe pro-growth and pro-metastatic functions of GPNMB to its ability to bind α5β1 integrin and increase downstream signaling in breast cancer cells. We show that GPNMB enhances breast cancer cell adhesion to fibronectin, increases α5β1 expression and associates with this receptor through its RGD motif. GPNMB recruitment into integrin complexes activates Src and Fak signaling pathways in an RGD-dependent manner. Importantly, both the RGD motif and cytoplasmic tail of GPNMB are required to promote primary mammary tumor growth; however, only mutation of the RGD motif impaired the formation of lung metastases. Together, these findings identify novel and distinct molecular mediators of GPNMB-induced breast cancer growth and metastasis.
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