Research Projects

• Liver cancer is the sixth leading cause of cancer, in which HCC is the most dominant one. The Hippo signaling pathway, an evolutionarily conserved signaling molecule, plays critical roles in organ size control and tumorigenesis. The aberrant activation of the transcriptional coactivator YAP or TAZ, downstream effectors of the Hippo signaling pathway, has been implicated in several human cancers including HCC. When Hippo pathway is ON, its human homologue Mst1and Mst2 phosphorylate Lats1/2, which in turn phosphorylates YAP/TAZ which ultimately leads to its proteasomal degradation and YAP remains in inactive form in cytoplasm. When Hippo pathway is OFF, YAP remains in active form and translocated to nucleus where it turns on pro-proliferative and pro-survival genes i.e., CTGF, ANKRD1, AXL and CYR61 enable cell proliferation. • Through previous studies it has been confirmed that YAP is overexpressed in HCC cells but its effects on tumor and its microenvironment is unknown during interaction between stromal (endothelial cells, macrophage, immune cells and stellate cells/ myofibroblast) and HCC cells. • We will characterize YAP mediated secretome from stromal cells via proteomic analysis and evaluate its effect on tumor microenvironment. Secretome comprises of proteins secreted by cells, including soluble factors, ECM, and proteins present in microvesicles/exosomes. • The proteomic analysis identified several proteins that revealed differences in the composition of the secretome obtained from cells during disease progression. Therefore, investigating differences in the secretome during disease progression can be a means of obtaining useful information, not only to improve the knowledge but also to identify key factors with potential clinical use.