RT Journal Article
SR Electronic
T1 Cancer cells resist mechanical destruction in the circulation via RhoA-myosin II axis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 601039
DO 10.1101/601039
A1 Devon L. Moose
A1 Benjamin L. Krog
A1 Lei Zhao
A1 Tae-Hyung Kim
A1 Sophia Williams-Perez
A1 Gretchen Burke
A1 Lillian Rhodes
A1 Marion Vanneste
A1 Patrick Breheny
A1 Mohammed Milhem
A1 Christopher S. Stipp
A1 Amy C. Rowat
A1 Michael D. Henry
YR 2019
UL http://biorxiv.org/content/early/2019/04/06/601039.abstract
AB During metastasis cancer cells are exposed to potentially destructive hemodynamic forces including fluid shear stress (FSS) while en route to distant sites. However, prior work indicates that cancer cells are more resistant to brief pulses of high-level fluid shear stress (FSS) in vitro relative to non-transformed epithelial cells. Herein we identify a mechanism of FSS resistance in cancer cells, and extend these findings to mouse models of circulating tumor cells (CTCs). We show that cancer cells acutely isolated from primary tumors are resistant to FSS. Our findings demonstrate that cancer cells activate the RhoA-myosin II axis in response to FSS, which protects them from FSS-induced plasma membrane damage. Moreover, we show that the myosin II activity is protective to CTCs in mouse models. Collectively our data indicate that viable CTCs actively resist destruction by hemodynamic forces and are likely to be more mechanically robust than is commonly thought.