Grant: Project Grant - PA - Breast Cancer Prevention & Early Detection

Rac1 controls many important cell functions and the aberrant activity of Rac1 needs to cancer and many other diseases. Due to its well-established role in cell structure and motility, efforts have been focused on the role of Rac1 in cancer cell migration and cancer metastasis. Indeed, Rac1 has been identified as an important regulator of cancer cell invasion and migration. Overexpression or mutation of Rac1 has shown to stimulate cancer metastasis. Despite significant evidence of the nuclear localization 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 gene expression through alternative 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 alternative splicing contribute to tumorigenesis and cancer 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.