Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy.
Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, Italy.
Int J Mol Sci. 2023 Jan 17;24(3):1823. doi: 10.3390/ijms24031823.
Nuclear factor-κB (NF-κB) transcription factors play a key role in the pathogenesis of multiple myeloma (MM). The survival, proliferation and chemoresistance of malignant plasma cells largely rely on the activation of canonical and noncanonical NF-κB pathways. They are triggered by cancer-associated mutations or by the autocrine and paracrine production of cytokines and growth factors as well as direct interaction with cellular and noncellular components of bone marrow microenvironment (BM). In this context, NF-κB also significantly affects the activity of noncancerous cells, including mesenchymal stromal cells (MSCs), which have a critical role in disease progression. Indeed, NF-κB transcription factors are involved in inflammatory signaling that alters the functional properties of these cells to support cancer evolution. Moreover, they act as regulators and/or effectors of pathways involved in the interplay between MSCs and MM cells. The aim of this review is to analyze the role of NF-κB in this hematologic cancer, focusing on NF-κB-dependent mechanisms in tumor cells, MSCs and myeloma-mesenchymal stromal cell crosstalk.
核因子-κB（NF-κB）转录因子在多发性骨髓瘤（MM）的发病机制中发挥着关键作用。恶性浆细胞的存活、增殖和化疗耐药性在很大程度上依赖于经典和非经典 NF-κB 途径的激活。这些途径可被癌症相关突变或细胞因子和生长因子的自分泌和旁分泌产生以及与骨髓微环境（BM）的细胞和非细胞成分的直接相互作用所触发。在这种情况下，NF-κB 还显著影响非癌细胞的活性，包括间充质基质细胞（MSCs），它们在疾病进展中起着关键作用。事实上，NF-κB 转录因子参与炎症信号转导，改变这些细胞的功能特性，以支持癌症的演变。此外，它们作为 MSCs 和 MM 细胞相互作用中涉及的途径的调节剂和/或效应物发挥作用。本文旨在分析 NF-κB 在这种血液系统癌症中的作用，重点关注肿瘤细胞、MSCs 和骨髓瘤-间充质基质细胞相互作用中 NF-κB 依赖性机制。
