Profilin as a target to suppress Invasive breast cancer

描述（由申请人提供）：拟议项目的总体目标是研究profilin-1（Pfn 1-一种细胞骨架调节蛋白）下调在乳腺癌中的功能意义。我们将研究Pfn 1，一种传统的促迁移分子，如何也可以调节在膜-胞质界面产生的细胞内信号传导，以抑制乳腺癌的侵袭和转移。在目标1中，我们将首先结合联合收割机临床相关性和小鼠模型研究，以确定a）Pfn 1失调和乳腺癌转移进展之间是否存在因果关系，以及B）Pfn 1表达是否反映肿瘤进展的阶段并预测乳腺癌患者的临床结果（目标1）。在目标2和3中，我们将确定Pfn 1抑制乳腺癌扩散的分子途径。这些研究的成功完成将确定Pfn 1是否可用作乳腺癌的预后标志物，并证明围绕Pfn 1的新型癌症治疗方法的合理性。 公共卫生相关性：乳腺癌在美国女性癌症死亡中排名第二。在这个项目中，我们研究了一种新的机制，如何profilin-1，一种传统的促迁移细胞骨架蛋白，调节信号在膜-胞质界面和抑制乳腺癌的侵袭和转移。这项研究的成功完成将产生对基本肿瘤细胞生物学的新见解，并提供导致进展的基本腺癌行为的分子基础。

DESCRIPTION (provided by applicant): The overall goal of the proposed project is to investigate the functional significance of profilin-1 (Pfn1 - a cytoskeleton regulatory protein) downregulation in breast cancer. We will study how Pfn1, a traditionally pro- migratory molecule, can also regulate intracellular signaling generated at the membrane-cytosol interface to suppress breast cancer invasion and metastasis. In Aim 1, we will first combine clinical correlation and mouse model studies to determine whether a) there is a casual relationship between Pfn1 dysregulation and metastatic progression of breast cancer, and b) Pfn1 expression reflects stages in tumor progression and predicts clinical outcome of breast cancer patients (Aim 1). In Aims 2 and 3, we will identify the molecular pathways by which Pfn1 inhibits breast cancer dissemination Successful completion of these studies will determine whether Pfn1 could be used as a prognostic marker in breast cancer and justify novel cancer therapeutics revolving around Pfn1. PUBLIC HEALTH RELEVANCE: Breast cancer ranks second among cancer deaths in women in the United States. In this project, we examine a novel mechanism of how profilin-1, a traditional pro-migratory cytoskeletal protein, regulates signaling at the membrane-cytosol interface and suppresses breast cancer invasion and metastasis. A successful completion of this study will yield novel insights into fundamental tumor cell biology and provide molecular underpinnings of basic adenocarcinoma behaviors that lead to progression.