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ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma
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 s...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326668/ https://www.ncbi.nlm.nih.gov/pubmed/30594912 http://dx.doi.org/10.18632/aging.101725 |
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author | Frezza, Valentina Fierro, Claudia Gatti, Elena Peschiaroli, Angelo Lena, Anna Maria Petruzzelli, Margherita Annicchiarico Candi, Eleonora Anemona, Lucia Mauriello, Alessandro Pelicci, Pier Giuseppe Melino, Gerry Bernassola, Francesca |
author_facet | Frezza, Valentina Fierro, Claudia Gatti, Elena Peschiaroli, Angelo Lena, Anna Maria Petruzzelli, Margherita Annicchiarico Candi, Eleonora Anemona, Lucia Mauriello, Alessandro Pelicci, Pier Giuseppe Melino, Gerry Bernassola, Francesca |
author_sort | Frezza, Valentina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6326668 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-63266682019-01-16 ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma Frezza, Valentina Fierro, Claudia Gatti, Elena Peschiaroli, Angelo Lena, Anna Maria Petruzzelli, Margherita Annicchiarico Candi, Eleonora Anemona, Lucia Mauriello, Alessandro Pelicci, Pier Giuseppe Melino, Gerry Bernassola, Francesca Aging (Albany NY) Research Paper 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. Impact Journals 2018-12-28 /pmc/articles/PMC6326668/ /pubmed/30594912 http://dx.doi.org/10.18632/aging.101725 Text en Copyright © 2018 Frezza et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Frezza, Valentina Fierro, Claudia Gatti, Elena Peschiaroli, Angelo Lena, Anna Maria Petruzzelli, Margherita Annicchiarico Candi, Eleonora Anemona, Lucia Mauriello, Alessandro Pelicci, Pier Giuseppe Melino, Gerry Bernassola, Francesca ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma |
title | ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma |
title_full | ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma |
title_fullStr | ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma |
title_full_unstemmed | ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma |
title_short | ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma |
title_sort | δnp63 promotes igf1 signalling through irs1 in squamous cell carcinoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326668/ https://www.ncbi.nlm.nih.gov/pubmed/30594912 http://dx.doi.org/10.18632/aging.101725 |
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