Kai FuiBoon, Laklai Hanane, Weaver Valerie M
Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Trends Cell Biol. 2016 Jul;26(7):486-497. doi: 10.1016/j.tcb.2016.03.007. Epub 2016 Apr 4.
Atherosclerosis, cancer, and various chronic fibrotic conditions are characterized by an increase in the migratory behavior of resident cells and the enhanced invasion of assorted exogenous cells across a stiffened extracellular matrix (ECM). This stiffened scaffold aberrantly engages cellular mechanosignaling networks in cells, which promotes the assembly of invadosomes and lamellae for cell invasion and migration. Accordingly, deciphering the conserved molecular mechanisms whereby matrix stiffness fosters invadosome and lamella formation could identify therapeutic targets to treat fibrotic conditions, and reducing ECM stiffness could ameliorate disease progression.
动脉粥样硬化、癌症和各种慢性纤维化疾病的特征是驻留细胞的迁移行为增加,以及各种外源性细胞在硬化的细胞外基质(ECM)中侵袭增强。这种硬化的支架异常地参与细胞中的细胞机械信号网络,促进侵袭小体和片状伪足的组装以实现细胞侵袭和迁移。因此,破译基质硬度促进侵袭小体和片状伪足形成的保守分子机制可以确定治疗纤维化疾病的治疗靶点,降低ECM硬度可以改善疾病进展。