Remarkable breakthroughs in our knowledge of cell and matrix mechanobiological signaling have advanced our understanding of breast tumorigenesis. However, our comprehension of the metastatic process, or the pathological spread of tumor cells, remains incomplete. Critical to advancing metastasis is the remodeling of the tumor-stroma boundary. The remodeling of this barrier to metastasis include mechanobiological contributions by stromal extracellular matrix proteins and breast tumor cells. I will discuss the development of model systems that use tools and techniques from the physical sciences to probe: (i) stromal matrix structure and mechanics, and (ii) collective cellular mechanics and migration. In particular, I will first discuss how the altered structure-function relationship of a critical extracellular matrix protein, fibronectin, promotes a tumor-permissive microenvironment. And then I will discuss how a physical unjamming transition, as predicted by changes in cell shape, might provide quiescent breast epithelial cells with the capacity to collectively migrate. These findings represent a novel, interdisciplinary endeavor that may have a significant impact on our understanding of the critical mechanobiological initiators that drive breast cancer metastasis and may contribute to the identification of new targeted therapies and strategies.
Dr. Karin Wang is a postdoctoral working with Dr. Fredberg at Harvard University. She received her Biomedical Engineering degrees from Stony Brook University in 2010 (B.E./M.S.) and from Cornell University in 2015 (Ph.D.). At Cornell, with Drs. Delphine Gourdon and Claudia Fischbach-Teschl, Dr. Wang used biomaterials tools and techniques to probe the mechanobiological function of fibronectin in the developing breast tumor stroma. For this research, she received awards and honors from various societies and conferences, such as the Society for Biomaterials and the ETS Trainee Award for the 10th World Biomaterials Congress. At Harvard, Dr. Wang’s current work focuses on developing model systems to biophysically probe the mechanobiological regulators that govern collective migration during breast tumorigenesis. For this research, she was awarded a NRSA (F32 Postdoctoral Fellowship) from the NIH/NCI, CMBE Rising Star Award, and BMES Career Development Award. Dr. Wang’s research program employs interdisciplinary approaches –integrating principles from engineering, biomaterials science, physics, and cell biology– to study the mechanobiological regulators that maintain homeostasis and drive disease progression.