Regulation of the Prenylation, Trafficking, and Activity of KRas and Rac1 by RabL3 in Breast Cancer

Project Description Narrative:

Breast cancer is the most common cancer in women both worldwide and in Wisconsin. The lifetime risk of being diagnosed with breast cancer is one in eight, and in 2023 alone, there is expected to be 5,460 new cases of breast cancer diagnosed and 720 breast cancer associated deaths in Wisconsin. This not only makes breast cancer the most common type of cancer diagnosed in women, but also the fourth most common cause of cancer associated deaths. In addition, incidence rates of breast cancer in Wisconsin increased 0.9% per year between 2015 and 2019, reflecting a greater increase than was seen in the United States overall during the same time period. The small GTPases KRas and Rac1 promote breast cancer malignancy and must localize at specific sites in breast cancer cells to activate the signaling cascades that induce breast cancer tumorigenesis and metastasis.

This project will examine mechanisms that control KRas and Rac1 localization in breast cancer cells to define new approaches to suppress breast cancer malignancy. These studies are highly relevant to health of Wisconsin communities, given the burden of breast cancer for women statewide.