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Oral Oncol. 2016 Sep;60:81-9. doi: 10.1016/j.oraloncology.2016.06.010. Epub 2016 Jul 15.

p38 MAPK mediates epithelial-mesenchymal transition by regulating p38IP and Snail in head and neck squamous cell carcinoma.

Author information

1
Lung Cancer Research Program of the Jonsson Comprehensive Cancer Center, United States; Division of Pulmonary and Critical Care Medicine, Department of Medicine, United States.
2
Department of Head and Neck Surgery, United States.
3
Department of Pathology and Laboratory Medicine, United States.
4
UCLA Head and Neck Cancer Program, United States.
5
Lung Cancer Research Program of the Jonsson Comprehensive Cancer Center, United States; Division of Pulmonary and Critical Care Medicine, Department of Medicine, United States; Department of Pathology and Laboratory Medicine, United States; Jonsson Comprehensive Cancer Center, United States; Department of Biostatistics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States; Veterans' Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States.
6
Department of Head and Neck Surgery, United States; Jonsson Comprehensive Cancer Center, United States; UCLA Head and Neck Cancer Program, United States. Electronic address: mstjohn@mednet.ucla.edu.

Abstract

BACKGROUND:

In the present study, we investigated the role of p38-p38IP signaling in the inflammation-induced promotion of epithelial-to-mesenchymal transition (EMT) in Head and Neck Squamous Cell Carcinoma (HNSCC).

METHODS:

Quantitative RT-PCR, western blot analysis, spheroid modeling and immunohistochemical staining of human HNSCC tissue sections were used.

RESULTS:

p38 inhibitor treated and p38 shRNA HNSCC cell lines demonstrate a significant upregulation in E-cadherin mRNA and a decrease in the mRNA expression of Snail. p38 binds to and stabilizes p38IP, a subunit of histone SPT3-TAF9-GCN5 acetyltransferase (STAGA), resulting in enhanced transcription of Snail. p38 shRNA HNSCC cell lines show a less invasive phenotype in a spheroid model. In clinical HNSCC samples, p38 interacting protein (p38IP) is significantly increased compared to adjacent normal tissue. An inverse relationship between p38, p38IP and E-cadherin is demonstrated.

CONCLUSIONS:

Herein we provide the first report that p38-p38IP is required for the Snail-induced E-cadherin down-regulation and cell invasion in HNSCC.

KEYWORDS:

EMT; HNSCC; Snail; p38; p38IP

[Indexed for MEDLINE]

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