ArticleBMC cancer2018
Neuropilin-1 promotes the oncogenic Tenascin-C/integrin β3 pathway and modulates chemoresistance in breast cancer cells.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- The extracellular matrix: structure, composition, biological functions, diseases, and therapeutic targets.Molecular biomedicine · 2026Review
- Preparation of Pluronic F127 hydrogel loaded with BIF1-iRGD recombinant protein for its targeted anti-cancer effects.Research in pharmaceutical sciences · 2025Article
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- Pan-cancer analysis of ITGB3 as a potential prognostic and immunological biomarker.Discover oncology · 2025Article
- Neuropilin-1: A Multifaceted Target for Cancer Therapy.Current oncology (Toronto, Ont.) · 2025Review
- Review
- Aidi injection inhibits the migration and invasion of gefitinib-resistant lung adenocarcinoma cells by regulating the PLAT/FAK/AKT pathway.Chinese medicine · 2025Article
- Understanding the role of TNFR2 signaling in the tumor microenvironment of breast cancer.Journal of experimental & clinical cancer research : CR · 2024Review
- Focus on Pancreatic Cancer Microenvironment.Current oncology (Toronto, Ont.) · 2024Review
- PEX3 promotes regenerative repair after myocardial injury in mice through facilitating plasma membrane localization of ITGB3.Communications biology · 2024Article
- Dissection of the signal transduction machinery responsible for the lysyl oxidase-like 4-mediated increase in invasive motility in triple-negative breast cancer cells: mechanistic insight into the integrin-β1-NF-κB-MMP9 axis.Frontiers in oncology · 2024Article
- The Nervous System Development Regulator Neuropilin-1 as a Potential Prognostic Marker and Therapeutic Target in Brain Cancer.Cancers · 2023Review
- Neuropilin-1 Knockout and Rescue Confirms Its Role to Promote Metastasis in MDA-MB-231 Breast Cancer Cells.International journal of molecular sciences · 2023Article
- ITGB3 promotes cisplatin resistance in osteosarcoma tumors.Cancer medicine · 2023Article
- miR-218 affects the ECM composition and cell biomechanical properties of glioblastoma cells.Journal of cellular and molecular medicine · 2022Article
- Article
- EZH2 engages TGFβ signaling to promote breast cancer bone metastasis via integrin β1-FAK activation.Nature communications · 2022Article
- The extracellular matrix molecule tenascin-C modulates cell cycle progression and motility of adult neural stem/progenitor cells from the subependymal zone.Cellular and molecular life sciences : CMLS · 2022Article
- Targeting of lactate dehydrogenase C dysregulates the cell cycle and sensitizes breast cancer cells to DNA damage response targeted therapy.Molecular oncology · 2022Article
- Long noncoding RNA RP11-70C1.3 confers chemoresistance of breast cancer cells through miR-6736-3p/NRP-1 axis.Bosnian journal of basic medical sciences · 2022Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundNeuropilin-1 (NRP-1), a non-tyrosine kinase glycoprotein receptor, is associated with poor prognosis breast cancer, however transcriptomic changes triggered by NRP-1 overexpression and its association with chemoresistance in breast cancer have not yet been explored.
methodsBT-474 NRP-1 variant cells were generated by stable overexpression of NRP-1 in the BT-474 breast cancer cell line. RNA sequencing and qRT-PCR were conducted to identify differentially expressed genes. The role of an upregulated oncogene, Tenascin C (TNC) and its associated pathway was investigated by siRNA-mediated knockdown. Resistant variants of the control and BT-474 NRP-1 cells were generated by sequential treatment with four cycles of Adriamycin/Cyclophosphamide (4xAC) followed by four cycles of Paclitaxel (4xAC + 4xPAC).
resultsNRP-1 overexpression increased cellular tumorigenic behavior. RNA sequencing identified upregulation of an oncogene, Tenascin-C (TNC) and downregulation of several tumor suppressors in BT-474 NRP-1 cells. Additionally, protein analysis indicated activation of the TNC-associated integrin β3 (ITGB3) pathway via focal adhesion kinase (FAK), Akt (Ser473) and nuclear factor kappa B (NF-kB) p65. siRNA-mediated TNC knockdown ablated the migratory capacity of BT-474 NRP-1 cells and inactivated FAK/Akt473 signaling. NRP-1 overexpressing cells downregulated breast cancer resistance protein (BCRP/ABCG2). Consequently, sequential treatment with Adriamycin/Cyclophosphamide (AC) cytotoxic drugs to generate resistant cells indicated that BT-474 NRP-1 cells increased sensitivity to treatment by inactivating NRP-1/ITGB3/FAK/Akt/NF-kB p65 signaling compared to wild-type BT-474 resistant cells.
conclusionsWe thus report a novel mechanism correlating high baseline NRP-1 with upregulated TNC/ITGB3 signaling, but decreased ABCG2 expression, which sensitizes BT-474 NRP-1 cells to Adriamycin/Cyclophosphamide. The study emphasizes on the targetability of the NRP-1/ITGB3 axis and its potential as a predictive biomarker for chemotherapy response.
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