CD30 Induces Heat Shock Protein 90 and Signal Integration in Classic Hodgkin Lymphoma Cells

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• 作者：Mariko Watanabe^&lowast ; ; Kazumi Nakano^&dagger ; ; Marshall E. Kadin^&Dagger ; ; Masaaki Higashihara^&lowast ; ; Toshiki Watanabe^&dagger ; ; Ryouichi Horie^&lowast ; ; ^§ ; ; ^{rhorie@med.kitasato-u.ac.jp}
• 刊名：The American Journal of Pathology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：187
• 期：1
• 页码：163-175
• 全文大小：2681 K
• 卷排序：187

文摘

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.