MYC deregulation is common in human cancer and has a role in sustaining the aggressive cancer stem cell populations. MYC mediates a broad transcriptional response controlling normal biological programmes, but its activity is not clearly understood. We address MYC function in cancer stem cells through the inducible expression of Omomyc—a MYC-derived polypeptide interfering with MYC activity—taking as model the most lethal brain tumour, glioblastoma. Omomyc bridles the key cancer stemlike cell features and affects the tumour microenvironment, inhibiting angiogenesis. This occurs because Omomyc interferes with proper MYC localization and itself associates with the genome, with a preference for sites occupied by MYC. This is accompanied by selective repression of master transcription factors for glioblastoma stemlike cell identity such as OLIG2, POU3F2, SOX2, upregulation of effectors of tumour suppression and differentiation such as ID4, MIAT, PTEN, and modulation of the expression of microRNAs that target molecules implicated in glioblastoma growth and invasion such as EGFR and ZEB1. Data support a novel view of MYC as a network stabilizer that strengthens the regulatory nodes of gene expression networks controlling cell phenotype and highlight Omomyc as model molecule for targeting cancer stem cells.

Resetting cancer stem cell regulatory nodes upon MYC inhibition / Galardi, S; Savino, M; Scagnoli, F; Pellegatta, S; Pisati, F; Zambelli, F; Illi, B; Annibali, D; Beji, S; Orecchini, E; Alberelli, Ma; Apicella, C; Fontanella, Ra; Michienzi, A; Finocchiaro, G; Farace, Mg; Pavesi, G; Ciafrè, Sa; Nasi, S. - In: EMBO REPORTS. - ISSN 1469-221X. - STAMPA. - 17:12(2016), pp. 1872-1889. [10.15252/embr.201541489]

Resetting cancer stem cell regulatory nodes upon MYC inhibition

Scagnoli, F;Annibali, D;Beji, S;Orecchini, E;Fontanella, Ra;Farace, Mg;Nasi, S
2016

Abstract

MYC deregulation is common in human cancer and has a role in sustaining the aggressive cancer stem cell populations. MYC mediates a broad transcriptional response controlling normal biological programmes, but its activity is not clearly understood. We address MYC function in cancer stem cells through the inducible expression of Omomyc—a MYC-derived polypeptide interfering with MYC activity—taking as model the most lethal brain tumour, glioblastoma. Omomyc bridles the key cancer stemlike cell features and affects the tumour microenvironment, inhibiting angiogenesis. This occurs because Omomyc interferes with proper MYC localization and itself associates with the genome, with a preference for sites occupied by MYC. This is accompanied by selective repression of master transcription factors for glioblastoma stemlike cell identity such as OLIG2, POU3F2, SOX2, upregulation of effectors of tumour suppression and differentiation such as ID4, MIAT, PTEN, and modulation of the expression of microRNAs that target molecules implicated in glioblastoma growth and invasion such as EGFR and ZEB1. Data support a novel view of MYC as a network stabilizer that strengthens the regulatory nodes of gene expression networks controlling cell phenotype and highlight Omomyc as model molecule for targeting cancer stem cells.
2016
MYC inhibition; omomyc; glioblastoma
01 Pubblicazione su rivista::01a Articolo in rivista
Resetting cancer stem cell regulatory nodes upon MYC inhibition / Galardi, S; Savino, M; Scagnoli, F; Pellegatta, S; Pisati, F; Zambelli, F; Illi, B; Annibali, D; Beji, S; Orecchini, E; Alberelli, Ma; Apicella, C; Fontanella, Ra; Michienzi, A; Finocchiaro, G; Farace, Mg; Pavesi, G; Ciafrè, Sa; Nasi, S. - In: EMBO REPORTS. - ISSN 1469-221X. - STAMPA. - 17:12(2016), pp. 1872-1889. [10.15252/embr.201541489]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/933364
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