Cortactin in HNSSC tumor progression

描述(申请人提供)：头颈部鳞状细胞癌(HNSCC)是全球第六大最常见的癌症，在美国每年有40,000例新病例和11,000例死亡。尽管进步提高了患者的生活质量，但在过去的30年里，患者的存活率几乎没有改善。在HNSCC中发生的遗传异常中，11q13扩增是最常见的之一，与预后不良和患者存活率下降密切相关。在该扩增子中促进肿瘤侵袭性的一个强有力的候选基因是Cortactin，一种促进细胞运动和侵袭的细胞骨架蛋白。从机制上讲，Cortactin是侵袭足细胞表面突起的重要组成部分，被认为与癌症的侵袭有关；然而，目前尚不清楚这种活动在多大程度上促进了体内肿瘤的生长和侵袭。我们研究的目的是测试皮质蛋白在11q13扩增的HNSCC肿瘤进展中的个体作用。通过利用逆转录病毒表达系统在未扩增和11q13扩增的HNSCC细胞系中操纵Cortactin的表达，我们将测试Cortactin在体内HNSCC肿瘤生长和侵袭中的作用以及体外侵袭活性。到授权期结束时，我们应该已经确定了1)Cortactin是否促进HNSCC肿瘤的进展，从而成为一个良好的治疗靶点；以及2)内陷活动和肿瘤生长之间是否存在更广泛的联系。

DESCRIPTION (provided by applicant): Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with 40,000 new cases and 11,000 deaths occurring each year in the United States. Despite advances that improve the quality of life for patients, there has been little to no improvement in survival for the last 30 years. Among the genetic aberrations that occur in HNSCC, 11q13 amplification is one of the most common and is strongly linked to poor prognosis and decreased survival of patients. A strong candidate gene within that amplicon to promote tumor aggressiveness is cortactin, a cytoskeletal protein that promotes cell motility and invasion. Mechanistically, cortactin is an essential component of invadopodia, cell surface protrusions thought to be involved in cancer invasion; however it is not clear to what extent this activity contributes to tumor growth and aggressiveness in vivo. The goal of our study is to test the individual role of cortactin in progression of 11q13-amplified HNSCC tumors. Through the use of retroviral expression systems to manipulate cortactin expression in non-amplified and 11q13-amplified HNSCC cell lines, we will test the role of cortactin in HNSCC tumor growth and invasion in vivo and invadopodia activity in vitro. By the end of the grant period, we should have determined 1) whether cortactin promotes HNSCC tumor progression and thus represents a good target for treatment; and 2) whether there is a more general link between invadopodia activity and tumor growth.