Actin cytoskeletal mediators of motility and invasion amplified and overexpressed in head and neck cancer

Abstract

Coordinated regulation of the actin cytoskeleton is central to cell motility, invasion and metastasis. Head and neck squamous cell carcinoma (HNSCC) is a highly invasive disease displaying frequent lymph node metastasis, compounding patient management. HNSCC progression is characterized by frequent amplification of chromosome segments 3q26-29, 8q23-24 and 11q13, events that are associated with poor patient outcome. The relative frequency of these amplification events and correlation with invasive disease raises the potential that these regions harbor actin regulatory genes important in facilitating reorganization of the actin cytoskeleton to promote tumor invasion. Identification of the actin cytoskeletal regulatory genes located within the 3q26-29, 8q23-24 and 11q13 amplicons will provide an important first step towards the comprehensive understanding of the molecular events that govern invasion and metastasis in HNSCC and other tumors containing these amplifications. We utilized Ensembl MartView to conduct a gene mining analysis within chromosome segments 3q26-29, 8q23-24 and 11q13 to identify known and predicted regulators of actin-based cell movement, tumor invasion and metastasis. All examined chromosomal regions contain genes known that regulate the actin cytoskeleton, with several (PI3-kinase alpha, focal adhesion kinase (FAK) and cortactin) known to promote invasion in HNSCC and other carcinomas. Additional genes known to regulate motility and invasion were also identified. Amplification of chromosome 3q26-29, 8q23-24 and 11q13 therefore results in known or predicted overexpression of several key mediators that can act alone or potentially act in concert to promote actin-based cell invasion in HNSCC and other cancer types.