Targeting oncogenic serine/threonine-protein kinase BRAF in cancer cells inhibits angiogenesis and abrogates hypoxia

摘要

Angiogenesis, the development of new blood vessels, is a pivotal process in tumor development. Understanding how individual genetic lesions affect angiogenesis is a fundamental, but largely unexplored, question. We report that activation of one oncogene, BRAF~(V600E), in the epithelium of a tumor modulates angiogenesis in the surrounding stromal (or connective tissue) cells. We further find that inhibiting BRAF in tumor cells with a specific drug influences the network of blood vessels of a tumor and abrogates oxygen deprivation, or hypoxia, caused by poor blood vessel growth (Fig. PI). This suggests that the "normal" tumor vascu-lature could be indirectly treated by targeting such a somatic genetic lesion.