Research Paper Volume 10, Issue 12 pp 4224—4240
ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma
- 1 Department of Experimental Medicine, TOR University of Rome "Tor Vergata", Rome 00133, Italy
- 2 Department of Experimental Oncology European Institute of Oncology, Milan 20139, Italy
- 3 National Research Council of Italy Institute of Translational Pharmacology (IFT-CNR), Rome 00133, Italy
- 4 Istituto Dermopatico dell'Immacolata, IRCCS,, Rome 00163, Italy
- 5 Medical Research Council, Toxicology Unit, University of Cambridge, Leicester LE1 9HN, UK
received: October 24, 2018 ; accepted: December 12, 2018 ; published: December 28, 2018 ;https://doi.org/10.18632/aging.101725
How to Cite
Copyright: Frezza et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.