HSP110 Inhibition in Primary Effusion Lymphoma Cells: One Molecule, Many Pro-Survival Targets
Author:
Gonnella Roberta1ORCID, Zarrella Roberta1, Di Crosta Michele1, Benedetti Rossella1ORCID, Arena Andrea1, Santarelli Roberta1ORCID, Gilardini Montani Maria Saveria1ORCID, D’Orazi Gabriella2ORCID, Cirone Mara1ORCID
Affiliation:
1. Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy 2. Department of Neurosciences, Imaging and Clinical Sciences, University G. d’Annunzio, 00131 Chieti, Italy
Abstract
Heat shock proteins (HSPs) are highly expressed in cancer cells and represent a promising target in anti-cancer therapy. In this study, we investigated for the first time the expression of high-molecular-weight HSP110, belonging to the HSP70 family of proteins, in Primary Effusion Lymphoma (PEL) and explored its role in their survival. This is a rare lymphoma associated with KSHV, for which an effective therapy remains to be discovered. The results obtained from this study suggest that targeting HSP110 could be a very promising strategy against PEL, as its silencing induced lysosomal membrane permeabilization, the cleavage of BID, caspase 8 activation, downregulated c-Myc, and strongly impaired the HR and NHEJ DNA repair pathways, leading to apoptotic cell death. Since chemical inhibitors of this HSP are not commercially available yet, this study encourages a more intense search in this direction in order to discover a new potential treatment that is effective against this and likely other B cell lymphomas that are known to overexpress HSP110.
Funder
Italian Association for Cancer Research ATENEO 2021
Subject
Cancer Research,Oncology
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