Abstract 4752: Cortactin and coronin 1B cooperate to promote tumor cell invasion in head and neck squamous cell carcinoma

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Abstract Amplification of chromosome 11q13 in head and neck squamous cell carcinoma (HNSCC) is a common occurrence associated with poor patient prognosis. Within the core amplified region is the gene that encodes cortactin (CTTN), a filamentous (F)- actin binding protein and Src kinase substrate that stabilizes Arp2/3-F-actin branchpoints in dynamic cortical F-actin structures. CTTN amplification results in increased lymph node metastases and decreased survival rates in HNSCC patients. CTTN amplification in HNSCC cell lines enhances tumor cell motility and invasion. Chromosomal regions of varying length flanking the core 11q13 amplicon are often amplified in HNSCC, and contain several genes with the potential to cooperate with CTTN in regulating actin dynamics. One of these genes within the 11q13 region outside of the core amplicon is CORO1B (coronin 1B), an actin-binding protein that antagonizes cortactin function by promoting the breakdown of cortactin-stabilized Arp2/3-F-actin branches, resulting in impaired cell motility. Here we show that coronin 1B is a potential mediator of HNSCC invasion. CORO1B amplification and overexpression occurs in a subset of HNSCC patients with CTTN amplification. Coronin 1B localizes with cortactin within HNSCC invadopodia, ventral membranous protrusions responsible for degrading extracellular matrix to facilitate loco-regional invasion and extracapsular spread. RNAi-mediated coronin 1B knockdown decreases the number of invadopodia per cell, enhances cell spreading and reduces extracellular matrix degradation. These results collectively point to a potential role for coronin 1B in regulating HNSCC tumor cell invasion through modulating cortactin activity and invadopodia function. Our data also support a potential diagnostic function for CORO1B amplification in denoting a previously unidentified HNSCC subset that may display increased invasiveness in cases containing 11q13 amplification. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4752. doi:10.1158/1538-7445.AM2011-4752