Profilin as a target to suppress Invasive breast cancer

描述(申请人提供)：拟议项目的总体目标是研究Profilin-1(PFN1-一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PFN1，一种传统上支持迁移的分子，如何也能调节在膜-胞浆界面产生的细胞内信号，以抑制乳腺癌的侵袭和转移。在目标1中，我们将首先结合临床相关性和小鼠模型研究，以确定a)PFN1失调与乳腺癌的转移进展之间是否存在因果关系，以及b)PFN1的表达反映了肿瘤进展的不同阶段并预测乳腺癌患者的临床结果(目标1)。在目标2和目标3中，我们将确定PFN1抑制乳腺癌扩散的分子途径成功完成这些研究将确定PFN1是否可以作为乳腺癌的预后标志，并证明以PFN1为中心的新型癌症疗法的合理性。

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.