Project 1: EMT and Tumor Progression
The epithelial mesenchymal transition (EMT) is thought to play an important role in the initial invasion during cancer metastasis. We are interested in understanding how cancer EMT contributes not only to cancer metastasis, but also to other phases of cancer progression, including early tumorigenesis and the dormant state of disseminated tumor cells (DTC), a phenomenon in which micrometastatic disease is present in multiple organs but remains quiescent and clinically undetectable.
Dormant DTCs are extremely rare and highly resistant to cancer therapies, representing a major obstacle to cancer elimination. Our lab has generated a genetic cancer EMT model and demonstrated that the critical EMT initiator factor Snail1 is necessary and sufficient for breast cancer EMT and metastasis, and that another key EMT factor Twist1 supplants Snail1 to maintain EMT’s transcriptional program in dormant DTCs until they reactivate growth to form macrometastases.
This knowledge could hold the key to developing strategies to reawaken dormant DTCs to re-sensitize them to therapies. Additionally, we study novel roles of EMT factors in mesenchymal transformation of cancer stem cells in several cancers including breast cancer and glioblastoma, a deadly type of brain cancer, and in regulation of the immune tumor microenvironment. The goal is to identify novel approaches to reprogram the immunosuppressive tumor microenvironment to improve response to immunotherapy and long-term survival.