Epithelial-Mesenchymal Plasticity in Carcinoma Metastasis

Friday, April 18, 2014 - 2:00pm
Fung Auditorium | Powell-Focht Bioengineering Hall
Jing Yang

Associate Professor of Pharmacology and Pediatrics 

University of California, San Diego

Epithelial-Mesenchymal Plasticity in Carcinoma Metastasis

Abstract: 
During metastasis, epithelial tumor cells dissociate from each other, disseminate into the systemic circulation, and then establish secondary tumors in distant sites. A developmental program termed Epithelial-Mesenchymal Transition (EMT) is implicated in promoting the dissemination of single carcinoma cells during metastasis. To understand the involvement of EMT in metastasis in vivo, we established a transgenic mouse model that expresses the EMT-inducing transcription factor Twist1 on the basal layer of the skin in an inducible fashion. We show that activation of Twist1 is sufficient to promote carcinoma cells to undergo EMT and disseminate into blood circulation. Twist1-mediated EMT is necessary for tumor cells to intravasate into the circulation as well as for extravasation of tumor cells out of the lung vasculature. Importantly, in distant sites, turning off Twist1 to allow reversion of EMT is essential for disseminated tumor cells to proliferate and form macrometastases. Together, these data indicate that EMT is dynamically regulated during tumor metastasis: carcinoma cells undergo EMT to disseminate; once reaching distant site, they need to revert to an epithelial identity to form macrometastases. Our ongoing studies aim to understand how EMT is dynamically regulated to impact EMT and tumor metastasis. Toward this goal, we have uncovered a new mechanotransduction pathway that responds to increasing matrix stiffness in the tumor microenvironment to activate Twist1 and drive EMT during breast tumor progression.
Bio: 

Jing Yang is an Associate Professor of Pharmacology and Pediatrics at University of California, San Diego. She did her undergraduate study at University of Science and Technology of China and then obtained her PhD in Molecular Cancer Biology at Duke in 1999. Her graduate research focused on understanding how regulated nuclear transport of the key mitotic regulators, the Cdc2/Cyclin B kinase and the Cdc25 phosphatase, directly impinged on control of entry into mitosis. In 2000, Dr. Yang became a Damon Runyon Cancer Research Foundation postdoctoral fellow with Dr. Robert Weinberg at Whitehead Institute for Biomedical Research and identified a critical role of the Twist1 transcription factor in tumor metastasis. Dr. Yang joined the faculty of University of California, San Diego as an Assistant Professor in 2006 and was promoted to Associate Professor with tenure in 2012.

Dr. Yang’s research focuses on understanding the molecular basis of tumor metastasis. Her laboratory combines cell and molecular biology tools, mouse tumor models, functional genomics, and 2D/3D imaging techniques to uncover the genes and the signaling pathways responsible for tumor metastasis. Her group has identified two cellular programs, Epithelial-Mesenchymal Transition (EMT) and invadopodia-mediated extracellular matrix degradation as being critical for tumor invasion and metastasis and continues to address the dynamic involvement of these programs in metastasis. Dr. Yang's achievements have been recognized by many awards, including NIH Director’s New Innovators Award, American Cancer Society Research Scholar, Kimmel Scholar award, and the Hartwell Foundation Investigator.