Grant: Project Grant - PA: Breast Cancer Research

Rac1, like other Rho GTPases, is involved in the acquisition of all the hallmarks of cancer. Rac1 is overexpressed or mutated in breast cancer and many other cancers. Rac1 signaling is also linked to many other diseases. Due to its well-established role in cytoskeleton dynamics, efforts have been focused on the role of Rac1 in cancer metastasis. Little is known regarding the role of Rac1 in gene expression and in tumorigenesis. Our overall goal is to identify novel nuclear function of Rac1 in regulating gene expressing and cell cycle progression and its relevance to breast cancer. Despite significant evidence of the nuclear localization of Rac1, studies have been focused on the extranuclear function of Rac1. The function of nuclear Rac1 has been rarely studied and is poorly understood. We have shown recently that nuclear Rac1 is localized to the nuclear speckles (NS) and regulates mRNA splicing. The aim of this proposed research is to uncover the novel functions of Rac1 in NS in the regulation of pre-mRNA splicing. We will also determine if the aberrant activity of Rac1 in NS and in pre-mRNA splicing contribute to tumorigenesis and progression. By extending Rac1 function beyond the cytoplasm to the nucleus, our study will not only change the paradigm of Rac1 research, but also identify novel target for breast cancer therapy.