2. Academic Validation
  3. Cdc42-mediated supracellular cytoskeleton induced cancer cell migration under low shear stress

Cdc42-mediated supracellular cytoskeleton induced cancer cell migration under low shear stress

  • Biochem Biophys Res Commun. 2019 Oct 29;519(1):134-140. doi: 10.1016/j.bbrc.2019.08.149.
Lingling Liu 1,  Hua Jiang 2,  Wei Zhao 1,  Yao Meng 1,  Ji Li 3,  Tongwei Huang 4,  Jinghui Sun 5
Affiliations

Affiliations

  • 1 School of Laboratory Medicine, Collaborative Innovation Center of Sichuan for Elderly Care and Health, Development and Regeneration Key Laboratory of Sichuan Province, Sichuan Provincial Engineering Laboratory for Prevention and Control Technology of Veterinary Drug Residue in Animal-origin Food, Chengdu Medical College, Chengdu, 610500, Sichuan, China.
  • 2 Department of Pediatrics, Department of Microbiology and Immunology, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • 3 Department of Clinical Laboratory, Sichuan GEM Flower Hospital, Chengdu, 610213, Sichuan, PR China.
  • 4 Department of Blood Transfusion, Ziyang Hospital of Traditional Chinese Medicine, Ziyang, 641300, Sichuan, PR China.
  • 5 School of Laboratory Medicine, Collaborative Innovation Center of Sichuan for Elderly Care and Health, Development and Regeneration Key Laboratory of Sichuan Province, Sichuan Provincial Engineering Laboratory for Prevention and Control Technology of Veterinary Drug Residue in Animal-origin Food, Chengdu Medical College, Chengdu, 610500, Sichuan, China. Electronic address: sunjhemail@163.com.
PMID: 31477271 DOI: 10.1016/j.bbrc.2019.08.149
Abstract

Tumor microenvironment is composed of biological, chemical and physical factors. Mechanical factors are more and more focused these years. Therefore, mimicking mechanical factors' contribution to Cancer cell malignancy will greatly improve the advance in this field. Although the induced malignant behaviors are present under many stimuli such as growth or inflammatory factors, the cell key physical migration mechanisms are still missing. In this study, we identify that low shear stress significantly promotes the formation of needle-shaped membrane protrusions, which is called filopodia and important for the sense and interact of a cell with extracellular matrix in the tumor microenvironment. Under low shear stress, the migration is promoted while it is inhibited in the presence of ROCK Inhibitor Y27632, which could abolish the F-actin network. Using cell imaging, we further unravel that key to these protrusions is Cell division cycle 42 (Cdc42) dependent. After Cdc42 activation, the filopodia is more and longer, acting as massagers to pass the information from a cell to the microenvironment for its malignant phenotype. In the Cdc42 inhibition, the filopodia is greatly reduced. Moreover, small GTPases Cdc42 rather than Rac1 and Rho directly controls the filopodia formation. Our work highlights that low shear stress and Cdc42 activation are sufficient to promote filopodia formation, it not only points out the novel structure for Cancer progression but also provides the experimental physical basis for the efficient drug anti-cancer strategies.

Keywords

Cdc42; Filopodia; Low shear stress; Mechanotransduction; Migration.

Figures
Products