HSPs/STAT3 Interplay Sustains DDR and Promotes Cytokine Release by Primary Effusion Lymphoma Cells.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

HSP27 Heat-Shock Proteins*/metabolism ; HSP70 Heat-Shock Proteins*/metabolism ; HSP90 Heat-Shock Proteins*/metabolism ; Lymphoma, Primary Effusion*/drug therapy ; Lymphoma, Primary Effusion*/genetics ; DNA Damage* ; Molecular Targeted Therapy*; Humans ; Apoptosis ; Cell Line, Tumor ; Cytokines ; STAT3 Transcription Factor/metabolism

Primary effusion lymphoma (PEL) is a rare and aggressive B-cell lymphoma, against which current therapies usually fail. In the present study, we show that targeting HSPs, such as HSP27, HSP70 and HSP90, could be an efficient strategy to reduce PEL cell survival, as it induces strong DNA damage, which correlated with an impairment of DDR. Moreover, as HSP27, HSP70 and HSP90 cross talk with STAT3, their inhibition results in STAT3 de-phosphorylation and. On the other hand, the inhibition of STAT3 may downregulate these HSPs. These findings suggest that targeting HSPs has important implications in cancer therapy, as it can reduce the release of cytokines by PEL cells, which, besides affecting their own survival, could negatively influence anti-cancer immune response.

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IG2019-23040 Italian Association for Cancer Research; 2017K55HLC Ministero della Salute

Keywords: DDR; HSP27; HSP70; HSP90; PEL; STAT3; cytokines

0 (Cytokines)
0 (HSP27 Heat-Shock Proteins)
0 (HSP70 Heat-Shock Proteins)
0 (HSP90 Heat-Shock Proteins)
0 (STAT3 protein, human)
0 (STAT3 Transcription Factor)

Date Created: 20230225 Date Completed: 20230331 Latest Revision: 20230331

20250114

PMC9959463

10.3390/ijms24043933

36835344