Oncogenic STRAP regulates c-Jun stability and persistent migration

Abstract

The serine threonine kinase receptor-associated protein (STRAP) is a WD40 domain protein that regulates a wide array of biological processes. Previous reports suggest that STRAP possesses oncogenic characteristics and regulates signaling pathways associated with tumorigenesis. The aim of this dissertation was to investigate the functional role of STRAP in cellular proliferation and motility. I have shown that STRAP expression in fibroblasts promotes expression of the c-Jun proto-oncogene by inhibiting ubiquitin-mediated proteolysis. Stabilization of c-Jun was associated with increased expression of the AP-1 target gene, cyclin D1, and increased proliferation. These findings may suggest that STRAP-mediated AP-1 signaling can support tumor growth through cell autonomous and paracrine signaling. With respect to cellular motility, I have shown that STRAP appears to regulate persistent chemotaxis and tail formation during motility. Loss of STRAP expression was associated with increased cellular adhesion as well as alterations in the size and distribution of focal adhesion kinase (FAK) complexes. The results of this study suggest that STRAP promotes efficient chemotaxis through modulation of directionality and adhesion dynamics. Taken together, these studies provide insight into the potential mechanisms by which STRAP can promote tumor growth and metastasis.