Tumor stiffness is unrelated to myosin light chain phosphorylation in cancer cells.
Many tumors are stiffer than their surrounding tissue. This increase in stiffness has been attributed, in part, to a Rho-dependent elevation of myosin II light chain phosphorylation. To characterize this mechanism further, we studied myosin light chain kinase (MLCK), the main enzyme that phosphorylates myosin II light chains. We anticipated that increases in MLCK expression and activity would contribute to the increased stiffness of cancer cells. However, we find that MLCK mRNA and protein levels are substantially less in cancer cells and tissues than in normal cells. Consistent with this observation, cancer cells contract 3D collagen matrices much more slowly than normal cells. Interestingly, inhibiting MLCK or Rho kinase did not affect the 3D gel contractions while blebbistatin partially and cytochalasin D maximally inhibited contractions. Live cell imaging of cells in collagen gels showed that cytochalasin D inhibited filopodia-like projections that formed between cells while a MLCK inhibitor had no effect on these projections. These data suggest that myosin II phosphorylation is dispensable in regulating the mechanical properties of tumors.
Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Hui-Jun
HJ
Yu
Leonid A
LA
Serebryannyy
Madeline
M
Fry
Madelyne
M
Greene
Olga
O
Chernaya
Wen-Yang
WY
Hu
Teng-Leong
TL
Chew
Nadim
N
Mahmud
Shrihari S
SS
Kadkol
Sarah
S
Glover
Gail
G
Prins
Zuzana
Z
Strakova
Primal
P
de Lanerolle
D008841:Actin Cytoskeleton / Q000378:metabolism; D001696:Biomechanical Phenomena; D045744:Cell Line, Tumor; D006801:Humans; D055595:Mechanical Phenomena; D018994:Myosin Light Chains / Q000378:metabolism*; D010766:Phosphorylation
D018994:Myosin Light Chains