ΔNp63 Promotes IGF1 Signalling Through IRS1 in Squamous Cell Carcinoma

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2018 Dec 31

PMID 30594912

Citations 9

Authors

Valentina Frezza

Claudia Fierro

Elena Gatti

Angelo Peschiaroli

Anna Maria Lena

Margherita Annicchiarico Petruzzelli

Eleonora Candi

Lucia Anemona

Alessandro Mauriello

Pier Giuseppe Pelicci

Gerry Melino

Francesca Bernassola

Affiliations

Soon will be listed here.

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.

Citing Articles

p63 orchestrates serine and one carbon metabolism enzymes expression in head and neck cancer.

Cappello A, Tosetti G, Smirnov A, Ganini C, Yang X, Shi Y Biol Direct. 2023; 18(1):73.

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Mutual connected IL-6, EGFR and LIN28/Let7-related mechanisms modulate PD-L1 and IGF upregulation in HNSCC using immunotherapy.

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Serine and one-carbon metabolism sustain non-melanoma skin cancer progression.

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Involvement of transcribed lncRNA uc.291 and SWI/SNF complex in cutaneous squamous cell carcinoma.

Mancini M, Cappello A, Pecorari R, Lena A, Montanaro M, Fania L Discov Oncol. 2022; 12(1):14.

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