Melanoma is one of the most immunogenic tumors and has the highest potential to elicit specific adaptive antitumor immune responses. Immune cells induce apoptosis of cancer cells either by soluble factors or by triggering cell-death pathways, particularly the TRAIL pathway. Melanoma cells exploit multiple mechanisms to escape immune system tumoricidal control. FKBP51 is a relevant pro-oncogenic factor of melanoma cells supporting NF-B-mediated resistance and cancer stemness/invasion epigenetic programs. We investigated whether FKBP51 was involved in TRAIL resistance.Using two different melanoma cell lines and 3 different methods for FKBP51 modulation, namely short interfering RNA (siRNA), short hairpin RNA (sh-RNA), and CRISPR/Cas9 KO, we show that FKBP51-silencing increased DR5 expression and enhanced sensitivity of melanoma cells to TRAIL-induced apoptosis. The mechanism of DR5 regulation involved the repressor activity of YY1 that was attenuated by FKBP51 silencing.

EPIGENETIC REGULATION OF TRAIL-R2 EXPRESSION IN MELANOMA BY THE PEPTIDYL-PROLYL-ISOMERASE FKBP51 / Romano, Mf; Romano, S; Tufano, M; Martinelli, R. - (2021). (Intervento presentato al convegno 61th Congress of the Italian Society of Biochemistry and Molecular Biology tenutosi a Virtuale nel 24 settembre 2021).

EPIGENETIC REGULATION OF TRAIL-R2 EXPRESSION IN MELANOMA BY THE PEPTIDYL-PROLYL-ISOMERASE FKBP51

Romano MF;Romano S;
2021

Abstract

Melanoma is one of the most immunogenic tumors and has the highest potential to elicit specific adaptive antitumor immune responses. Immune cells induce apoptosis of cancer cells either by soluble factors or by triggering cell-death pathways, particularly the TRAIL pathway. Melanoma cells exploit multiple mechanisms to escape immune system tumoricidal control. FKBP51 is a relevant pro-oncogenic factor of melanoma cells supporting NF-B-mediated resistance and cancer stemness/invasion epigenetic programs. We investigated whether FKBP51 was involved in TRAIL resistance.Using two different melanoma cell lines and 3 different methods for FKBP51 modulation, namely short interfering RNA (siRNA), short hairpin RNA (sh-RNA), and CRISPR/Cas9 KO, we show that FKBP51-silencing increased DR5 expression and enhanced sensitivity of melanoma cells to TRAIL-induced apoptosis. The mechanism of DR5 regulation involved the repressor activity of YY1 that was attenuated by FKBP51 silencing.
2021
EPIGENETIC REGULATION OF TRAIL-R2 EXPRESSION IN MELANOMA BY THE PEPTIDYL-PROLYL-ISOMERASE FKBP51 / Romano, Mf; Romano, S; Tufano, M; Martinelli, R. - (2021). (Intervento presentato al convegno 61th Congress of the Italian Society of Biochemistry and Molecular Biology tenutosi a Virtuale nel 24 settembre 2021).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/873848
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