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

Carla Guarnotta, Claudio Tripodo, Roberta Zappasodi, Massimo Di Nicola, Alessandro M. Gianni, Lorenzo Castagnoli, Alessandra Cavanè, Giusi Ruggiero, Antonello D. Cabras, Monica Tortoreto, Bruno Venerando, Serenella M. Pupa, Filippo De Braud, Cristina Tringali, Nadia Zaffaroni

Risultato della ricerca: Articlepeer review

21 Citazioni (Scopus)

Abstract

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 104 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.
Lingua originaleEnglish
pagine (da-a)1768-1771
Numero di pagine4
RivistaBlood
Volume125
Stato di pubblicazionePublished - 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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