How does the VASH2 targeting therapy work? (Part 3)

VASH2 has various actions, and the whole mechanism has not been clarified yet. We have shown that the effect of VASH2 on metastasis is related to "epithelial-mesenchymal transition (EMT)", but there are other factors that cause EMT, and this alone should not be a characteristic feature of VASH2. Rather, we are now paying attention to "tubulin carboxypeptidase", which is an enzymatic that removes tyrosine residue (detyrosination) at the carboxyl terminus of α-tubulin that constitutes the cytoskeleton called microtubules.

Cytoskeleton is a general term for proteins that regulate the shape of cells. Among them, microtubes regulate cell division and cell motility, and also function as rails for proteins to move within cells. Tubulin, which constitutes microtubules, undergoes several modifications such as phosphorylation and acetylation, but detyrosination is the specific type of modification that occurs only in tubulin. In relation to cancer, cancers with a higher amount of "detyrosinated tubulin" are shown to be more malignant, and tubulin detyrosination is shown to be involved in the formation of cell projections necessary for cancer metastasis But, the true nature of tubulin carboxypeptidase has been unknown for a long time. Recently, however, an enzyme-like structure was found in the Vasohibin molecule, which was subsequently found to have tubulin carboxypeptidase activity. Thus, the missing link between cancer cells, tubulin detyrosination and cancer metastasis was connected by VASH2, and the significance of VASH2 target therapy became clear.