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Tumor metastasis is a complex, multi-step process by which cancer cells spread from a primary site to distant organs and establish secondary tumors. Although tumor metastasis causes over 90% of cancer deaths, little is known about its molecular basis. Dr. Yang's laboratory is using functional genomics, cellular and molecular biology approaches in cell culture, and mouse tumor models to uncover the genes and the signaling pathways responsible for tumor metastasis.
Our studies discovered that the Twist transcription factor, a master regulator of early embryonic morphogenesis, is essential for the ability of breast tumor cells to metastasize from the mammary gland to the lung. We further demonstrated that Twist activates epithelial-mesenchymal transition (EMT) to promote cell-cell dissociation and induces invadopodia formation to promote matrix degradation. Our and several other studies also reported the involvement of Twist and the EMT program in various aggressive human malignancies.
Currently, our research focuses on the following areas:
1) The Molecular Machinery: Twist, as a key player in tumor metastasis, may exploit several transcription targets to provoke EMT and other aspects of migration and invasion. We use genomics, bioinformatics, and biochemical approaches to dissect the signaling and effector pathways regulating EMT, invadopodia-mediated matrix degradation, and tumor metastasis. We then test the involvement of these signaling pathways in clinical human tumor samples.
2) The Dynamic Action: Our recent studies show that EMT plays a dynamic role during tumor metastasis. We have established several mouse models to label migrating tumor cells in vivo and to determine how activation of Twist and EMT contribute to tumor metastasis.
3) The Inducing Signals: The ability of carcinoma cells to undergo EMT and metastasize depends on both their genetic/epigenetic alternations and the environmental cues they receive. We are very interested in exploring the roles of such signals in inducing EMT and tumor metastasis.
4) The Novel Players: Our previous study identified a number of new candidate genes involved in tumor metastasis. We will explore their biological functions in tumor metastasis using cell culture models, mouse tumor models, and clinical human tumor samples.
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