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.

Galardi, S., Savino, M., Scagnoli, F., Pellegatta, S., Pisati, F., Zambelli, F., et al. (2016). Resetting cancer stem cell regulatory nodes upon MYC inhibition. EMBO REPORTS [10.15252/embr.201541489].

Resetting cancer stem cell regulatory nodes upon MYC inhibition.

GALARDI, SILVIA;ORECCHINI, ELISA;MICHIENZI, ALESSANDRO;CIAFRE', SILVIA ANNA;
2016-12-01

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.
dic-2016
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/13 - BIOLOGIA APPLICATA
Settore BIO/11 - BIOLOGIA MOLECOLARE
English
Con Impact Factor ISI
Galardi, S., Savino, M., Scagnoli, F., Pellegatta, S., Pisati, F., Zambelli, F., et al. (2016). Resetting cancer stem cell regulatory nodes upon MYC inhibition. EMBO REPORTS [10.15252/embr.201541489].
Galardi, S; Savino, M; Scagnoli, F; Pellegatta, S; Pisati, F; Zambelli, F; Illi, B; Annibali, D; Beji, S; Orecchini, E; Alberelli, M; Fontanella, R; M...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/170204
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