Rhoa-myosin II pathway confers resistance to fluid shear stress

• Main Author: Moose, Devon Lyle
• Other Authors: Henry, Michael D.
• Format: Others
• Language: English
• Published: University of Iowa 2018
• Subjects: Biophysics
• Online Access: https://ir.uiowa.edu/etd/6221; https://ir.uiowa.edu/cgi/viewcontent.cgi?article=7553&context=etd

The second leading cause of death in the United States is cancer, and approximately 90% of cancer related deaths are due to metastasis. When cancer metastasizes, cell from the tumor enter the circulation where they are exposed to hemodynamic forces. One of the main mechanical forces of the circulation is fluid shear stress (FSS), which was thought to be the main reason for metastatic inefficacy. However, recent studies have shown that in vitro cancer cells are more resistant to FSS than non-transformed epithelial cells. Additionally, that loss of viability cancer cells experience is biphasic in nature. Investigations into this adaptive response have shown that the Young’s Modulus of cancer cells is increased. Further investigating the adaptive phenomena, RhoA activity is shown to be increased in cancer cells and not non-transformed cells after exposure to two brief pulses of FSS. Also, extracellular calcium is also essential to maintain resistance upon exposure to FSS, although, through unknown mechanisms. Additionally, inhibiting myosin II sensitizes cell to FSS both in vivo and in vitro.