Conserved Cancer Cell Migration and Transcriptional Responses Encoded by 3D Extracellular Matrix Architecture

Friday, June 2, 2017 -
2:00pm to 3:00pm
The FUNG Auditorium
Stephanie Fraley

Assistant Professor of Bioengineering

University of California, San Diego

Conserved Cancer Cell Migration and Transcriptional Responses Encoded by 3D Extracellular Matrix Architecture

Cells interact closely with the extracellular matrix (ECM), which provides mechanical and chemical cues that influence cell behavior. The topographical organization of the ECM has been implicated in locally guiding cell migration both in healthy and disease states. In cancer, ECM organization independently predicts progression to metastasis. However, it remains unclear whether ECM architecture directly promotes acquisition of a metastatic migration phenotype or simply correlates with tumor progression. Using matrix engineering techniques to investigate the influence of 3D collagen architecture on cancer cell migration, we find that matrices with small pores and short fibers trigger a conserved transcriptional response and subsequent motility switch in multiple cancer cell types that is independent of matrix stiffness and hypoxia. The new migration mode results in cellular network formation, an aggressive clinical phenotype that is correlated with advanced metastatic disease in over 16 cancers but is poorly understood. The upregulated gene module is enriched for migration and vascluogenesis-associated genes that predict poor survival in patient data across six tumor types. Our findings identify a novel matrix-induced migration program and suggest that this program may be broadly relevant as a driver of metastasis in solid human cancers.

Dr. Stephanie Fraley joined UC San Diego in July 2014 as an assistant professor of Bioengineering. She earned her B.S. in Chemical Engineering in 2006 from The University of Tennessee Chattanooga and her Ph.D. in Chemical and Biomolecular Engineering in 2011 from The Johns Hopkins University. For her graduate work, she was awarded an NSF Graduate Research Fellowship, National Tau Beta Pi Fellowship, and was an Achievement Rewards for College Scientists Scholar, Johns Hopkins Heath Fellowship, National Siebel Scholarship, and ASEE/NSF Engineering Innovations Fellowship. Dr. Fraley then joined the Emergency Medicine department at The Johns Hopkins University as a postdoctoral fellow where she developed novel technological approaches to sensitively detect and quantitatively identify genetic material circulating in the bloodstream. Recently, she received a National Burroughs Wellcome Fund Career Award at the Scientific Interface for her research merging clinical diagnostic and basic research approaches. She is also a Kavli Frontiers of Science Fellow and recipient of an NSF CAREER award.