Metastasis, development of resistance to treatments, and tumor relapse are fundamental reasons for most cancer patient-related mortality. In my laboratory, we aim to understand the fundamental biology of cancer progression and, in particular, to comprehend how tumors become highly aggressive, develop resistance to therapies, and eventually become metastatic.
We and others have demonstrated that the aberrant activation of a latent embryonic program—known as the epithelial-mesenchymal transition (EMT), makes the cancer cells migratory, invasive, and metastatic (Yang and Mani et al., Cell 2004; Mani & Yang et al., PNAS 2007). Tumors at the metastatic site tend to appear similar to the primary tumor. Because EMT is necessary for cancer cells to migrate and invade, we demonstrated that the EMT program also provides stem cell properties to differentiated cancer cells (Mani et al., Cell 2008), which helps cancer cells to survive in circulation and establish metastasis in the hostile distant microenvironment. This highly cited and extremely influential article suggested that the tumor can make its own cancer stem cells by activating EMT and also explained the presence of plasticity within the tumor.
At present, we are pursuing the following areas.