Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: IRAK1 is a novel DEK transcriptional target and is essential for head and neck cancer cell survival.

Authors: Adams, Allie K; Bolanos, Lyndsey C; Dexheimer, Phillip J; Karns, Rebekah A; Aronow, Bruce J; Komurov, Kakajan; Jegga, Anil G; Casper, Keith A; Patil, Yash J; Wilson, Keith M; Starczynowski, Daniel T; Wells, Susanne I

Published In Oncotarget, (2015 Dec 22)

Abstract: The chromatin-binding DEK protein was recently reported to promote the growth of HPV+ and HPV- head and neck squamous cell carcinomas (HNSCCs). Relevant cellular and molecular mechanism(s) controlled by DEK in HNSCC remain poorly understood. While DEK is known to regulate specific transcriptional targets, global DEK-dependent gene networks in HNSCC are unknown. To identify DEK transcriptional signatures we performed RNA-Sequencing (RNA-Seq) in HNSCC cell lines that were either proficient or deficient for DEK. Bioinformatic analyses and subsequent validation revealed that IRAK1, a regulator of inflammatory signaling, and IRAK1-dependent regulatory networks were significantly repressed upon DEK knockdown in HNSCC. According to TCGA data, 14% of HNSCC specimens overexpressed IRAK1, thus supporting possible oncogenic functions. Furthermore, genetic or pharmacologic inhibition of IRAK1 in HNSCC cell lines was sufficient to attenuate downstream signaling such as ERK1/2 and to induce HNSCC cell death by apoptosis. Finally, targeting DEK and IRAK1 simultaneously enhanced cell death as compared to targeting either alone. Our findings reveal that IRAK1 promotes cell survival and is an attractive therapeutic target in HNSCC cells. Thus, we propose a model wherein IRAK1 stimulates tumor signaling and phenotypes both independently and in conjunction with DEK.

PubMed ID: 26527316 Exiting the NIEHS site

MeSH Terms: Blotting, Western; Carcinoma, Squamous Cell/genetics; Carcinoma, Squamous Cell/metabolism; Carcinoma, Squamous Cell/pathology*; Cell Survival/physiology; Chromosomal Proteins, Non-Histone/genetics; Chromosomal Proteins, Non-Histone/metabolism*; Flow Cytometry; Gene Expression Regulation, Neoplastic/physiology*; Gene Knockdown Techniques; Gene Regulatory Networks; Head and Neck Neoplasms/genetics; Head and Neck Neoplasms/metabolism; Head and Neck Neoplasms/pathology*; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; Immunoprecipitation; Interleukin-1 Receptor-Associated Kinases/genetics; Interleukin-1 Receptor-Associated Kinases/metabolism*; Oligonucleotide Array Sequence Analysis; Oncogene Proteins/genetics; Oncogene Proteins/metabolism*; Poly-ADP-Ribose Binding Proteins; Polymerase Chain Reaction; Squamous Cell Carcinoma of Head and Neck

Back
to Top