Cancer Cell Invasion and Metastasis

描述（由申请人提供）：癌症转移是癌症死亡的主要原因。理解癌症转移的分子基础的一个主要挑战是确定将细胞转换为转移状态的潜在分子变化。癌症侵袭和转移是一个复杂的过程，其涉及肿瘤细胞彼此之间以及与它们的微环境的物理偶联的协调变化，降解细胞外基质从而促进侵袭的细胞外蛋白酶的活化，以及导致肿瘤扩散或转移的细胞运动性的诱导。细胞通过从细胞的前缘延伸板状伪足来迁移。在侵袭性癌细胞中，片状伪足不同于非癌细胞。此外，侵袭性癌细胞还产生侵袭伪足，一种类似于板状伪足的结构，其促进癌细胞通过组织的侵袭。我们的长期目标是开发消除或阻断癌细胞侵袭和转移的策略。为了实现这一目标，我们建议从侵袭性癌细胞中纯化板状伪足和侵袭伪足，并对每个“结构”进行蛋白质组学分析。通过鉴定细胞蛋白（及其响应环境或致癌信号的翻译后修饰），招募到浸润性癌细胞的前沿板状伪足和侵袭伪足中，我们将大大增加我们对癌细胞运动性和侵袭性的理解，并有助于开发干预措施以消除癌细胞转移。

DESCRIPTION (provided by applicant): Cancer metastasis is the leading cause of cancer deaths. A major challenge to understanding the molecular basis for cancer metastasis has been to identify underlying molecular changes that switch cells to a metastatic state. Cancer invasion and metastasis is a complex process that involves coordinated changes in the physical coupling of tumor cells to one another and to their microenvironment, activation of extracellular proteases that degrade the extracellular matrix hereby facilitating invasion, and the induction of cell motility leading to spread or metastasis of the tumor. Cells migrate by extending lamellipodia from the forward leading edge of cells. In invasive cancer cells lamellipodia differ from non-cancer cells. In addition invasive cancer cells also produce invadopodia, a structure similar to lamellipodia that facilitates invasion of cancer cells through tissues. Our long-term goal is to develop strategies to abrogate or block cancer cells invasion and metastasis. Towards the achievement of this goal we propose to purify lamellipodium and invadopodium from invasive cancer cells, and perform a proteomic analysis of each "structure". Through the identification of the cellular proteins (and their post-translational modifications in response to environmental or oncogenic signals) recruited into the leading edge lamellipodia and invadopodia of invasive cancer cells we will greatly increase our understanding of cancer cell motility and invasiveness, and assist in the development of interventions to abrogate cancer cell metastasis.