【报  告  人】谭又华博士 美国香港理工大学助理教授
　　【时　　　  间】 2018年04月15日（周日）上午8:00
　　【地　　　  点】 科大西区力二楼215多媒体教室

摘要：

It is known that genetic and biochemical factors regulate various cellular functions and become dysfunctional in pathologic conditions. Accumulating evidence has demonstrated the significance of mechanical forces in biology. However, their roles in tumorigenesis remain unclear. We recently developed a mechanical strategy for selecting tumorigenic cancer stem cells (CSCs) from a pool of cancer cells by culturing single cancer cells in 3D soft fibrin matrices. The selected cells expressed stem cell genes, resisted to chemotherapy, and exhibited low stiffness and non-stiffening responses on substrates with increasing rigidity. Remarkably, as few as 10 such cells were able to survive and form tumors at the site of injection or at the lungs of wild-type mice. We further explored the mechanisms underlying the high tumorigenecity of these selected CSCs. When re-plated back to rigid substrates, the selected CSCs exhibited plasticity in Cdc42-mediated mechanical stiffening, histone 3 lysine residue 9 (H3K9) methylation, Sox2 expression, and self-renewal capability. In contrast to stiff matrices, soft fibrin matrices decreased focal adhesion kinase activity, H3K9 methylation, and promoted Sox2 expression. Mechanistically, H3K9 methylation at the Sox2 promoter region inhibited Sox2 expression that was essential in maintaining self-renewal capability of CSCs both in vitro and in vivo. In summary, we have demonstrated that 3D soft fibrin matrices can select and grow tumorigenic CSCs and that their self-renewal property is regulated by H3K9 demethylation and Sox2 upregulation mediated by matrix softness. These findings indicate that mechanical forces may regulate the plasticity of cancer cells.

报告人简介

Dr. Tan obtained his Bachelor and PhD degree from University of Science and Technology of China and City University of Hong Kong, respectively. He joined the Department of Biomedical Engineering at the Hong Kong Polytechnic University as Assistant Professor from 2015, before which he completed his postdoctoral fellowship in University of Illinois at Urbana-Champaign. His main research interests include mechanobiology, cell mechanics, and mechano-oncology.