Rapamycin promotes autophagy cell death of Kaposi's sarcoma cells through P75NTR activation.

Autor: Lupinacci S; Department of Nephrology, Dialysis and Transplantation, 'Kidney and Transplantation' Research Centre, Annunziata Hospital, Cosenza, Italy., Perri A; Department of Nephrology, Dialysis and Transplantation, 'Kidney and Transplantation' Research Centre, Annunziata Hospital, Cosenza, Italy., Toteda G; Department of Nephrology, Dialysis and Transplantation, 'Kidney and Transplantation' Research Centre, Annunziata Hospital, Cosenza, Italy., Vizza D; Department of Nephrology, Dialysis and Transplantation, 'Kidney and Transplantation' Research Centre, Annunziata Hospital, Cosenza, Italy., Lofaro D; Department of Nephrology, Dialysis and Transplantation, 'Kidney and Transplantation' Research Centre, Annunziata Hospital, Cosenza, Italy., Pontrelli P; Nephrology Unit, Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, Bari, Italy., Stallone G; Nephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy., Divella C; Nephrology Unit, Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, Bari, Italy., Tessari G; Section of Dermatology and Venereology, University-Hospital of Verona, Verona, Italy., La Russa A; Department of Nephrology, Dialysis and Transplantation, 'Kidney and Transplantation' Research Centre, Annunziata Hospital, Cosenza, Italy., Zaza G; Renal Unit, Department of Medicine, University-Hospital of Verona, Verona, Italy., Bonofiglio R; Department of Nephrology, Dialysis and Transplantation, 'Kidney and Transplantation' Research Centre, Annunziata Hospital, Cosenza, Italy.
Jazyk: angličtina
Zdroj: Experimental dermatology [Exp Dermatol] 2022 Feb; Vol. 31 (2), pp. 143-153. Date of Electronic Publication: 2021 Aug 14.
DOI: 10.1111/exd.14438
Abstrakt: The mammalian target of rapamycin inhibitor (mTOR-I) Rapamycin, a drug widely used in kidney transplantation, exerts important anti-cancer effects, particularly in Kaposi's Sarcoma (KS), through several biological interactions. In this in vivo and in vitro study, we explored whether the activation of the autophagic pathway through the low-affinity receptor for nerve growth factor, p75 NTR , may have a pivotal role in the anti-cancer effect exerted by Rapamycin in S. Our Kimmunohistochemistry results revealed a significant hyper-activation of the autophagic pathway in KS lesions. In vitro experiments on KS cell lines showed that Rapamycin exposure reduced cell viability by increasing the autophagic process, in the absence of apoptosis, through the transcriptional activation of p75 NTR via EGR1. Interestingly, p75 NTR gene silencing prevented the increase of the autophagic process and the reduction of cell viability. Moreover, p75 NTR activation promoted the upregulation of phosphatase and tensin homolog (PTEN), a tumour suppressor that modulates the PI3K/Akt/mTOR pathway. In conclusion, our in vitro data demonstrated, for the first time, that in Kaposi's sarcoma, autophagy triggered by Rapamycin through p75 NTR represented a major mechanism by which mTOR inhibitors may induce tumour regression. Additionally, it suggested that p75 NTR protein analysis could be proposed as a new potential biomarker to predict response to Rapamycin in kidney transplant recipients affected by Kaposi's sarcoma.
(© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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