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.

Expression of Abl interactor 1 and its prognostic significance in breast cancer: a tissue-array-based investigation

“…The vital role of actin cytoskeleton-associated proteins in cancer metastasis and invasion has been recognized and an array of implicated proteins has been recently identified [41,42]. Among them, Abi1 has been found to be critical in actin polymerization, lamellipodia formation, and cell migration [6][7][8]43].…”

Microtentacles Tip the Balance of Cytoskeletal Forces in Circulating Tumor Cells

“…The degree of actin crosslinking is directly implicated in CTC deformation., As malignancy progresses, the F-to-G actin ratio decreases, indicating a less polymerized actin cytoskeleton (20). Mutation in or altered expression of mediators of actin polymerization can also disrupt actin organization and crosslinking (21), which may weaken the cortical integrity. When microtubules are stabilized in concert with reduced actin integrity, CTCs produce increased McTNs (7, 8).…”

Development of monoclonal antibodies for the identification of novel invasion associated targets in human cancer

“…Stabilisation of the protrusive structures is achieved through integrin-mediated binding to the ECM of the actin cytoskeleton. This serves the additional role of co-ordinating signal transduction events that regulate cell movement (Kelley et al, 2008).…”

“…This severing activity has a dual effect on actin dynamics to promote cortical actin-based protrusions: the number of available barbed ends increase, thus allowing for rapid actin polymerisation at the cell cortex, independent of Arp2/3 complex activity. It also serves to boost F-actin depolymerisation, therefore utilising G-actin monomers in a further round of polymerisation (Kelley et al, 2008).…”

“…Cortactin, along with the non-receptor tyrosine kinase Src, and the membrane bound MT1-MMP plays an essential role in the formation and function of invadopodia. Integrins, such as αvβ3, in conjunction with their cytoplasmic interaction partners, are situated in the adhesive ring where they can mediate adhesion (Kelley et al, 2008). (Yilmaz et al, 2009).…”