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ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma
- Source :
- Aging (Albany NY), Aging (Albany, N.Y. Online) 10 (2018): 4224–4240. doi:10.18632/aging.101725, info:cnr-pdr/source/autori: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/titolo:?Np63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma/doi:10.18632%2Faging.101725/rivista:Aging (Albany, N.Y. Online)/anno:2018/pagina_da:4224/pagina_a:4240/intervallo_pagine:4224–4240/volume:10
- Publication Year :
- 2018
-
Abstract
- Accumulating evidence has proved that deregulation of ?Np63 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 ?Np63 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 ?Np63 in HNSSC may act as an oncogenic stimulus by altering the IGF signalling pathway.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Aging
IRS1
medicine.medical_treatment
Settore MED/08
Biology
p53 family, p63, IGF system, IRS1, head and neck tumours
Phosphatidylinositol 3-Kinases
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
medicine
Humans
Insulin
Insulin-Like Growth Factor I
Protein kinase B
PI3K/AKT/mTOR pathway
Mitogen-Activated Protein Kinase Kinases
p63
Effector
Settore BIO/11
Tumor Suppressor Proteins
Growth factor
Cell Biology
IGF system
head and neck tumours
Hedgehog signaling pathway
Gene Expression Regulation, Neoplastic
stomatognathic diseases
Insulin receptor
030104 developmental biology
030220 oncology & carcinogenesis
Carcinoma, Squamous Cell
Insulin Receptor Substrate Proteins
Cancer research
biology.protein
p53 family
Proto-Oncogene Proteins c-akt
Research Paper
Transcription Factors
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Aging (Albany NY), Aging (Albany, N.Y. Online) 10 (2018): 4224–4240. doi:10.18632/aging.101725, info:cnr-pdr/source/autori: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/titolo:?Np63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma/doi:10.18632%2Faging.101725/rivista:Aging (Albany, N.Y. Online)/anno:2018/pagina_da:4224/pagina_a:4240/intervallo_pagine:4224–4240/volume:10
- Accession number :
- edsair.doi.dedup.....6a4535c0fd29b18ffaf93721da6ba259