Polarity Establishment in Yeast

描述（由申请人提供）：Cdc42在细胞朝向多种信号（例如，T细胞向抗原呈递细胞极化，纤维化向伤口部位极化，或酵母芽形成）。人CDC42可以在功能上取代其酵母对应物，这表明Cdc42的关键功能是高度保守的，并且能够应用遗传、生物化学和细胞生物学方法使酵母成为描绘Cdc42在细胞极化中的作用机制的非常强大的系统。这项研究的目的是了解Cdc42的极化是如何调节的，以及这个过程是如何被限制的，以至于细胞只形成一个极化“前沿”。 癌细胞显示细胞形状，细胞间粘附和细胞运动性（所有肌动蛋白依赖性过程由Cdc42调节）的改变，这可能对恶性转化的许多方面都很重要。哺乳动物细胞中Cdc42的失调促进了锚定非依赖性生长，并且对于Ras转化细胞中发生的形态变化（以及锚定非依赖性）是必要的。因此，Cdc42失调影响癌细胞的增殖以及转移潜力。了解Cdc42的正常调节和功能是解决其失调如何促进癌症的重要第一步。

DESCRIPTION (provided by applicant): Cdc42 plays a key role in the polarization of cells towards a variety of signals (e.g., T cell polarization towards antigen-presenting cells, fibroblas polarization towards wound sites, or yeast bud formation). Human CDC42 can functionally substitute for its yeast counterpart, suggesting that key functions of Cdc42 have been highly conserved, and the ability to apply genetic, biochemical, and cell biological approaches makes yeast a very powerful system for delineating the mechanism of Cdc42 action in cell polarization. The goal of the proposed research is to understand how Cdc42 polarization is regulated, and how the process is restricted so that cells only form one polarization "front". Cancer cells display alterations of cell shape, cell-cell adhesion, and cell motility (all actin-dependent processes regulated by Cdc42), which are likely to be important for numerous aspects of malignant transformation. Deregulation of Cdc42 in mammalian cells promotes anchorage-independent growth, and is necessary for the morphological changes (as well as anchorage independence) that occur in Ras-transformed cells. Thus, Cdc42 deregulation affects the proliferation as well as the metastatic potential of cancer cells. Understanding the normal regulation and function of Cdc42 is an important first step towards addressing how their misregulation might promote cancer.