This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cancer is responsible for one in four deaths in the United States, the second most common cause of mortality. Most of the morbidity and mortality caused by cancer can be attributed to metastasis, the spread or movement of cancer cells from its origin to other areas of the body. Two of the earliest requirements in metastasis are that cancer cells must be able to move (migrate), and then break through the meshwork of molecules surrounding the cells (invade) to be able to spread to different areas of the body. If one can understand the mechanisms that contribute to cancer cell migration and invasion, one has a potential drug target that may impede or eliminate cancer growth and spread. The focus of this project is to characterize the role of the lysyl oxidase like-2 (LOXL2) protein in cancer cell migration and invasion. We have looked at many cancer tissues and found that the tissues with more LOXL2 protein are associated with markers of poorer prognosis. We have shown that the LOXL2 protein is only present in highly invasive/ metastatic breast cancer cell lines. Poorly invasive/non-metastatic breast cancer cell lines have no LOXL2 protein. We have developed poorly invasive/non-metastatic breast cancer cell lines which permanently produce LOXL2 protein in order to evaluate if the presence of LOXL2 will enable the cells to migrate and invade through a synthetic meshwork of molecules called Matrigel. We will also silence the expression of LOXL2 in highly invasive/metastatic breast cancer cell lines to evaluate if the absence of LOXL2 will render the cells unable to migrate or invade. We will also evaluate if catalytic activity and certain protein domains are important in the role of LOXL2 in migration and invasion.
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