Inhibitor of EMT
A frequent complication of recurrent cancer is the spread of the primary tumor to other secondary sites, a process called metastasis. The molecular mechanisms responsible for the occurrence of metastatic cancer are beginning to be elucidated with the identification of key regulators. Increasing evidence points to tumor cell epithelial-to-mesenchymal transition (EMT) as an important contributing process to metastatic evolution. The occurrence of EMT during tumor progression permits epithelial tumor cells, that are noninvasive and non-metastatic, to move from the primary tumor, invade the surrounding tissue, enter the bloodstream, and finally disseminate to, and proliferate at, secondary sites. In addition, epithelial cancer cells that undergo EMT adopt a behavior that is very similar to cancer stem cells including an inherent resistance to chemo- and radiotherapy. Thus, the discovery of proteins that directly participate and promote EMT may represent new targets to increase the sensitivity of tumors to chemotherapy and prevent the spread of primary tumors cells to other sites.
By mining the microarray data obtained from cell-based models of EMT, a critical downstream effector of EMT, called secreted clusterin (sCLU) was identified. The functional relevance of sCLU was demonstrated in not only its capacity to promote EMT by itself, but additionally, antibodies that interact with a specific region of sCLU can effectively neutralize EMT in vitro and in vivo.