Vascular Diseases in Cancer
Cancer progresses through several steps characterized by a conversion of normal tissue states to anaplasia and neoplasia. While the tumor continues to grow in a conducive environment, it draws leash of blood vessels along with it. Angiogenesis, a process of generation of novel blood vessels is fundamental during the development and in various diseases such as cancer. Wnt signaling, a highly conserved oncogenic pathway, is critical in angiogenesis. Beta-catenin is the prime mediator of Wnt activation. Focusing on the ubiquitination and proteasomal degradation of beta-catenin, our previous work has described Jade-1, as an ubiquitin ligase of wild-type beta catenin. Our recent efforts have specifically focused on c-Cbl as an E3 ligase for the mutant beta-catenin and the transcriptionally active beta-catenin in the nucleus. These two species of beta-catenin, once considered resistant to degradation, are the key mediators of tumorigenesis and are effectively downregulated by c-Cbl. Thus, c-Cbl is a unique E3 ligase of tumorigenic beta catenin, which is involved in several cancers including colorectal cancer pathogenesis. Leveraging the cancer animal models and human cancer samples including machine-learning based quantitative histology techniques, our group investigates the colorectal cancer pathogenesis to gain a deeper understanding of the role of E3 ligases of beta-catenin E3 ligases in various cancers.