多发性骨髓瘤（MM）是一种具有侵袭性的恶性肿瘤，在其进展过程中形成了一种有利于肿瘤生长的微环境，其特点是脐带间充质干细胞（MSCs）的蛋白质分泌和基因表达发生改变。反过来，MM患者的MSCs可以表现出较高的肿瘤促进活性，并发挥强大的免疫抑制作用。我们在此首次展示了与健康供体（HD）来源的MSCs相比，MM来源的MSCs具有更高的细胞活动性，并且伴随FilaminA（FLNA）的激活。此外，我们提出了IRE1a-FLNA轴参与调控MSC迁移过程的可能性。因此，IRE1a可以作为MM治疗的一个良好靶点，考虑到它在MM微环境中的促存活、促破骨细胞和化疗耐药作用。我们的结果表明，IRE1a的下调还可能干扰MSC对MM刺激的反应，可能防止细胞-细胞黏附介导的耐药性。此外，进一步探索IRE1a-FLNA相互作用可能提高MSC作为先进疗法应用中的细胞产品的寻位效率。

Multiple myeloma (MM) is an aggressive malignancy that shapes, during its progression, a pro-tumor microenvironment characterized by altered protein secretion and the gene expression of mesenchymal stem cells (MSCs). In turn, MSCs from MM patients can exert an high pro-tumor activity and play a strong immunosuppressive role. Here, we show, for the first time, greater cell mobility paralleled by the activation of FilaminA (FLNA) in MM-derived MSCs, when compared to healthy donor (HD)-derived MSCs. Moreover, we suggest the possible involvement of the IRE1a-FLNA axis in the control of the MSC migration process. In this way, IRE1a can be considered as a good target candidate for MM therapy, considering its pro-survival, pro-osteoclast and chemoresistance role in the MM microenvironment. Our results suggest that IRE1a downregulation could also interfere with the response of MSCs to MM stimuli, possibly preventing cell-cell adhesion-mediated drug resistance. In addition, further investigations harnessing IRE1a-FLNA interaction could improve the homing efficiency of MSC as cell product for advanced therapy applications.