CD30 induces heat shock protein 90 and signal integration in classic Hodgkin lymphoma cells
CD30 induces heat shock protein 90 and signal integration in classic Hodgkin lymphoma cells
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CD30 在经典霍奇金淋巴瘤细胞中诱导热休克蛋白 90 和信号整合
DOI：
10.1016/j.ajpath.2016.09.007
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发表时间：
2017
期刊：
影响因子：
6
通讯作者：
Horie R
中科院分区：
文献类型：
--
作者：
Watanabe M;Nakano K;Kadin ME;Higashihara M;Watanabe T;Horie R
先前的研究报告了经典霍奇金淋巴瘤（cHL）细胞中多种信号通路的失调。然而，这些途径如何整合的机制尚未完全了解。在此，我们发现cHL标志性抗原CD30参与了这一过程。CD30促进热休克因子1的磷酸化，激活热休克启动子元件，并诱导热休克蛋白（HSP）90。CD30抑制和随后的HSP 90抑制cHL细胞系中的NF-κ B、细胞外信号调节激酶、AKT和STAT途径。因此，CD30介导的HSP90诱导似乎是cHL细胞内信号整合的中心枢纽。我们还表明，CD30诱导热休克因子1通过c-Jun N-末端激酶在cHL细胞的磷酸化热休克蛋白90。虽然间变性大细胞淋巴瘤（ALCL）也与CD30过表达有关，但我们的实验表明，ALCL携带核磷蛋白间变性淋巴瘤激酶（ALK）中的HSP90诱导不依赖于CD30，而是通过c-Jun N-末端激酶依赖于ALK。总之，这些结果强调了CD 30在介导cHL细胞信号通路整合方面的新作用，同时在ALCL细胞中该功能被ALK取代。
Previous studies report deregulation of multiple signaling pathways in classic Hodgkin lymphoma (cHL) cells. However, the mechanisms of how these pathways are integrated are not fully understood. Herein, we show involvement of cHL hallmark antigen CD30 in this process. CD30 facilitates phosphorylation of heat shock factor 1, activates heat shock promoter element, and induces heat shock protein (HSP) 90. CD30 repression and subsequent inhibition of HSP90 suppresses NF-κB, extracellular signal-regulated kinase, AKT, and STAT pathways in cHL cell lines. Thus, CD30-mediated induction of HSP90 appears to serve as a central hub for integration of intracellular signaling in cHL cells. We also show that CD30 induces HSP90 through phosphorylation of heat shock factor 1 via c-Jun N-terminal kinase in cHL cells. Although anaplastic large-cell lymphoma (ALCL) also is associated with CD30 overexpression, our experiments reveal that HSP90 induction in ALCL-bearing nucleophosmin–anaplastic lymphoma kinase (ALK) does not depend on CD30 but instead on ALK via c-Jun N-terminal kinase. Together, these results highlight a novel role for CD30 in mediating integration of signaling pathways of cHL cells while being replaced in this function by ALK in ALCL cells.