Accumulating evidence has proved that deregulation of ΔNp63 expression plays an oncogenic role in head and neck squamous cell carcinomas (HNSCCs). Besides p63, the type 1-insulin-like growth factor (IGF) signalling pathway has been implicated in HNSCC development and progression. Most insulin/IGF1 signalling converges intracellularly onto the protein adaptor insulin receptor substrate-1 (IRS-1) that transmits signals from the receptor to downstream effectors, including the PI3K/AKT and the MAPK kinase pathways, which, ultimately, promote proliferation, invasion, and cell survival. Here we report that p63 directly controls IRS1 transcription and cellular abundance and fosters the PI3K/AKT and MAPK downstream signalling pathways. Inactivation of ΔNp63 expression indeed reduces tumour cell responsiveness to IGF1 stimulation, and inhibits the growth potential of HNSCC cells. In addition, a positive correlation was observed between p63 and IRS1 expression in human HNSCC tissue arrays and in publicly available gene expression data. Our findings indicate that aberrant expression of ΔNp63 in HNSSC may act as an oncogenic stimulus by altering the IGF signalling pathway.

Frezza, V., Fierro, C., Gatti, E., Peschiaroli, A., Lena, A., Petruzzelli, M., et al. (2018). ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma. AGING, 10(12), 4224-4240 [10.18632/aging.101725].

ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma

Frezza V
Membro del Collaboration Group
;
Fierro C
Membro del Collaboration Group
;
Candi E
Membro del Collaboration Group
;
Anemona L
Membro del Collaboration Group
;
Mauriello A
Membro del Collaboration Group
;
Melino G
Membro del Collaboration Group
;
Bernassola F.
Membro del Collaboration Group
2018-12-01

Abstract

Accumulating evidence has proved that deregulation of ΔNp63 expression plays an oncogenic role in head and neck squamous cell carcinomas (HNSCCs). Besides p63, the type 1-insulin-like growth factor (IGF) signalling pathway has been implicated in HNSCC development and progression. Most insulin/IGF1 signalling converges intracellularly onto the protein adaptor insulin receptor substrate-1 (IRS-1) that transmits signals from the receptor to downstream effectors, including the PI3K/AKT and the MAPK kinase pathways, which, ultimately, promote proliferation, invasion, and cell survival. Here we report that p63 directly controls IRS1 transcription and cellular abundance and fosters the PI3K/AKT and MAPK downstream signalling pathways. Inactivation of ΔNp63 expression indeed reduces tumour cell responsiveness to IGF1 stimulation, and inhibits the growth potential of HNSCC cells. In addition, a positive correlation was observed between p63 and IRS1 expression in human HNSCC tissue arrays and in publicly available gene expression data. Our findings indicate that aberrant expression of ΔNp63 in HNSSC may act as an oncogenic stimulus by altering the IGF signalling pathway.
dic-2018
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/11 - BIOLOGIA MOLECOLARE
Settore MED/08 - ANATOMIA PATOLOGICA
English
Con Impact Factor ISI
p53 family, p63, IGF system, IRS1, head and neck tumours
Frezza, V., Fierro, C., Gatti, E., Peschiaroli, A., Lena, A., Petruzzelli, M., et al. (2018). ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma. AGING, 10(12), 4224-4240 [10.18632/aging.101725].
Frezza, V; Fierro, C; Gatti, E; Peschiaroli, A; Lena, A; Petruzzelli, M; Candi, E; Anemona, L; Mauriello, A; Pelicci, P; Melino, G; Bernassola, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/236392
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