HSPH1 inhibition downregulates Bcl-6 and c-Myc and hampers the growth of human aggressive B-cell non-Hodgkin lymphoma

被引：46

作者：

Zappasodi, Roberta ^{[1
]}

Ruggiero, Giusi ^{[1
]}

Guarnotta, Carla ^{[2
]}

Tortoreto, Monica ^{[3
]}

Tringali, Cristina ^{[4
]}

Cavane, Alessandra ^{[1
]}

Cabras, Antonello D. ^{[5
]}

Castagnoli, Lorenzo ^{[6
]}

Venerando, Bruno ^{[4
]}

Zaffaroni, Nadia ^{[3
]}

Gianni, Alessandro M. ^{[1
,7
]}

De Braud, Filippo ^{[1
]}

Tripodo, Claudio ^{[2
]}

Pupa, Serenella M. ^{[6
]}

Di Nicola, Massimo ^{[1
]}

机构：

[1] Fdn IRCCS Ist Nazl Studio & Cura Tumori, Dept Med Oncol, Milan, Italy

[2] Univ Palermo, Sch Med, Human Pathol Sect, Tumor Immunol Unit,Dept Hlth Sci, Palermo, Italy

[3] Fdn IRCCS Ist Nazl Studio & Cura Tumori, Dept Expt Oncol, Mol Pharmacol Unit, Milan, Italy

[4] Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy

[5] Fdn IRCCS Ist Nazl Studio & Cura Tumori, Dept Med Oncol, Pathol Unit, Milan, Italy

[6] Fdn IRCCS Ist Nazl Studio & Cura Tumori, Dept Expt Oncol, Mol Targeting Unit, Milan, Italy

[7] Univ Milan, Med Oncol, Milan, Italy

来源：

BLOOD | 2015年 / 125卷 / 11期

关键词：

HSP105 FAMILY PROTEINS; EXPRESSION; ANGIOGENESIS; PATHOGENESIS; APOPTOSIS; THERAPY;

D O I：

10.1182/blood-2014-07-590034

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We have shown that human B-cell non-Hodgkin lymphomas (B-NHLs) express heat shock protein (HSP) H1/105 in function of their aggressiveness. Here, we now clarify its role as a functional B-NHL target by testing the hypothesis that it promotes the stabilization of key lymphoma oncoproteins. HSPH1 silencing in 4 models of aggressive B-NHLs was paralleled by Bcl-6 and c-Myc downregulation. In vitro and in vivo analysis of HSPH1-silenced Namalwa cells showed that this effect was associated with a significant growth delay and the loss of tumorigenicity when 10 4 cells were injected into mice. Interestingly, we found that HSPH1 physically interacts with c-Myc and Bcl-6 in both Namalwa cells and primary aggressive B-NHLs. Accordingly, expression of HSPH1 and either c-Myc or Bcl-6 positively correlated in these diseases. Our study indicates that HSPH1 concurrently favors the expression of 2 key lymphoma oncoproteins, thus confirming its candidacy as a valuable therapeutic target of aggressive B-NHLs.

引用

页码：1768 / 1771

页数：4

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