Liu Sisi, Wu Xiaoan, Yu Yang, Wen Xiongwei, Yu Zhang, Feng Xi-Qiao, Zhao Hucheng
Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, P. R. China.
Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, Florida 33136, United States.
ACS Biomater Sci Eng. 2020 Aug 10;6(8):4623-4630. doi: 10.1021/acsbiomaterials.0c00366. Epub 2020 Jul 30.
Cancer stem cells (CSCs) play a critical role in the cancer metastasis and account for tumor heterogeneity. Growing evidence indicates that the CSC phenotypes are related to the tumor microenvironment. In this study, we report that the gradient of mechanical stresses guides the spatial patterning of the expression of CD44 and Yes-associated protein (YAP) in the geometrically confined multicellular sheets. Our study shows that the cytoskeletal contraction regulates the expression of CD44 through the translocation of YAP into the nucleus. The results demonstrate that geometric confinement and mechanical stresses are the regulators in the spatial patterning of CSC. It may help to understand the relationship between the tumor microenvironment and oncogenesis.
癌症干细胞（CSCs）在癌症转移中起关键作用，并导致肿瘤异质性。越来越多的证据表明，癌症干细胞表型与肿瘤微环境有关。在本研究中，我们报告机械应力梯度在几何受限的多细胞层中引导CD44和Yes相关蛋白（YAP）表达的空间模式。我们的研究表明，细胞骨架收缩通过YAP易位进入细胞核来调节CD44的表达。结果表明，几何限制和机械应力是癌症干细胞空间模式的调节因子。这可能有助于理解肿瘤微环境与肿瘤发生之间的关系。
