The Study Of The Mechanism Of P55PIK Promoting Tumor Angiogenensis

Angiogenesis plays a key process in the tumor growth; vascular growth factor (VEGF) is an important mediator of angiogenesis. PI3K plays essential roles in angiogenesis, however, however, the mechanisms and specific functions of individual isoforms of PI3K members in tumor angiogenesis regulation are still not folly understood. In this study, we try to evaluate the role of p55PIK, a PI3K regulatory subunit encoded by PIK3R3gene, in tumor angiogenesis. We found that overexpressing p55PIK in cancer cells could up-regulate HIF-1α expression and promoted VEGF expression. Furthermore, over-expressing p55PIK promoted tumor angiogenesis in vivo and in vitro. Moreover, data indicated enhanced HIF-la expression by p55PIK-PI3K depended on its ability to activate NF-κB signaling pathway, especially to increase the phosphorylation of p65subunits of NF-κB, but not AKT or ERK signaling. Our study showed p55PIK-PI3K was essential in regulating cancer cells-mediated angiogenesis and contributed to tumor growth and that the p55PIK provides a potential and specific target for new anti-angiogenesis drug development.