RIP2 enhances cell survival by activation of NF-ĸB in triple negative breast cancer cells
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Elsevier B.V.
Abstract
Receptor-interacting protein 2 (RIP2) is an essential mediator of inflammation and innate immunity, but little is known about its role outside the immune system. Recently, RIP2 has been linked to chemoresistance of triple negative breast cancer (TNBC), the most aggressive breast cancer subtype for which there is an urgent need for targeted therapies. In this study we show that high expression of RIP2 in breast tumors correlates with a worse prognosis and a higher risk of recurrence. We also demonstrate that RIP2 confers TNBC cell resistance against paclitaxel and ceramide-induced apoptosis. Overexpression of RIP2 lead to NF-κB activation, which contributed to higher expression of pro-survival proteins and cell survival. Conversely, RIP2 knockdown inhibited NF-κB signaling, reduced levels of anti-apoptotic proteins and sensitized cells to drug treatment. Together, these data show that RIP2 promotes survival of breast cancer cells through NF-κB activation and that targeting RIP2 may be therapeutically beneficial for treatment of TNBC. © 2018
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Apoptosis, Nf-κb (nuclear factor κ-light-chain-enhancer of activated b cells), Rip2 (receptor-interacting serine-threonine kinase-2), Tnbc (triple negative breast cancer), Antineoplastic agents, Cell survival, Ceramides, Female, Humans, Mcf-7 cells, Nf-kappa b, Paclitaxel, Receptor-interacting protein serine-threonine kinase 2, Treatment outcome, Triple negative breast neoplasms, Tumor cells, cultured, Actin, Binding protein, Cell protein, Ceramide, Immunoglobulin enhancer binding protein, Nerve growth factor, Oncoprotein, Protein bax, Protein bcl 2, Protein bcl xl, Protein ciap1, Protein ciap2, Receptor interacting protein 2, Unclassified drug, X linked inhibitor of apoptosis, Antineoplastic agent, Receptor interacting protein serine threonine kinase 2, Ripk2 protein, human, Article, Breast cancer cell line, Cancer resistance, Cell protection, Cell viability, Controlled study, Human, Human tissue, Mda-mb-231 cell line, Overall survival, Priority journal, Protein expression, Signal transduction, Upregulation, Mcf-7 cell line, Metabolism, Pathology, Triple negative breast cancer, Tumor cell culture