Death of multiple myeloma cells induced by cAMP-signaling involves downregulation of Mcl-1 via the JAK/STAT pathway
Death of multiple myeloma cells induced by cAMP-signaling involves downregulation of Mcl-1 via the JAK/STAT pathway
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DOI：
10.1016/j.canlet.2013.02.042
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发表时间：
2013-07-28
期刊：
影响因子：
9.7
通讯作者：
Blomhoff, Heidi Kiil
中科院分区：
文献类型：
--
作者：
Follin-Arbelet, Virginie;Torgersen, Maria Lyngaas;Blomhoff, Heidi Kiil
持续寻找用于治疗多发性骨髓瘤（MM）的新治疗靶点。我们研究了cAMP诱导人MM细胞凋亡的机制，cAMP增加剂迅速抑制JAK 1及其底物STAT 3的活化。与作为Mcl-1转录调节因子的STAT 3一致，该促存活因子的表达被快速且选择性地降低。值得注意的是，外源性白细胞介素-6既不能阻止JAK 1/STAT 3的抑制，也不能阻止cAMP诱导的MM细胞的死亡。我们的研究结果表明，cAMP介导的MM细胞杀伤涉及JAK/STAT通路的抑制，使cAMP通路成为MM治疗的有希望的靶点。（c）2013 Elsevier爱尔兰Ltd.保留所有权利。
There is a continuous search for new therapeutic targets for treatment of multiple myeloma (MM). Here we investigated the mechanisms involved in cAMP-induced apoptosis of human MM cells, cAMP-increasing agents rapidly inhibited activation of JAK1 and its substrate STAT3. In line with STAT3 being a regulator of Mcl-1 transcription, the expression of this pro-survival factor was rapidly and selectively reduced. Notably, exogenous interleukin-6 neither prevented the inhibition of JAK1/STAT3 nor the death of MM cells induced by cAMP. Our results suggest that cAMP-mediated killing of MM cells involves inhibition of the JAK/STAT pathway, making the cAMP-pathway a promising target for treatment of MM. (c) 2013 Elsevier Ireland Ltd. All rights reserved.