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.
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