Decreased ferroportin promotes myeloma cell growth and osteoclast differentiation.
Decreased ferroportin promotes myeloma cell growth and osteoclast differentiation.
复制标题
DOI：
10.1158/0008-5472.can-14-3804
复制
发表时间：
2015-06-01
期刊：
影响因子：
11.2
通讯作者：
Zhan F
中科院分区：
文献类型：
--
作者：
Gu Z;Wang H;Xia J;Yang Y;Jin Z;Xu H;Shi J;De Domenico I;Tricot G;Zhan F
铁稳态在多发性骨髓瘤中被破坏，这是一种难以治愈的浆细胞恶性肿瘤，伴有溶解性骨病变。在这里，我们系统地分析了铁基因的表达特征，并证明了铁输出铁转运蛋白（FPN1）的mRNA表达在骨髓瘤细胞中显著下调，并与临床预后呈负相关。恢复FPN1的表达可减少细胞内易损铁池，抑制STAT3-MCL-1信号，抑制骨髓瘤细胞生长。此外，我们证明FPN1 mRNA在破骨细胞分化的初始阶段也下调，并通过调节铁调节剂TFRC、NF-κB和JNK途径抑制骨髓瘤细胞诱导的破骨细胞分化。总之，我们证明了FPN1的下调在促进多发性骨髓瘤细胞生长和骨吸收中起关键作用。
Iron homeostasis is disrupted in multiple myeloma, a difficult-to-cure plasma cell malignancy with lytic bone lesions. Here, we systematically analyzed iron gene expression signature and demonstrated that mRNA expression of iron exporter ferroportin (FPN1) is significantly downregulated in myeloma cells and correlates negatively with clinic outcome. Restoring expression of FPN1 reduces intracellular liable iron pool, inhibits STAT3-MCL-1 signaling, and suppresses myeloma cells growth. Furthermore, we demonstrated that mRNA of FPN1 is also downregulated at the initial stages of osteoclast differentiation and suppresses myeloma cell–induced osteoclast differentiation through regulating iron regulator TFRC, NF-κB, and JNK pathways. Altogether, we demonstrated that downregulation of FPN1 plays critical roles in promoting myeloma cell growth and bone resorption in multiple myeloma.