A. Panc10.05 tissue spheroids grown, stained with
phalloidin, and imaged in 3D (Matrigel) or 2D (collagen) show dissemination,
exacerbated in myosin IIA knockdown. Myosin IIC depletion suppresses
dissemination and generates actin cortical belts. 4-HAP induces actin belts in
control and myosin IIA-depleted spheroids. These belts are already present in
myosin IIC-depleted spheroids. Scale bar, 40 μm (confocal); 10 μm
(SIM). B. Quantification of these actin structures using normalized
standard deviation of pixel intensity; see Methods. Medians
plotted; p values on graphs. C. Endogenous myosin
IIA in AsPC-1 cells localizes on actin stress fibers; myosin IIC localizes to
the actin cortex. D. 4-HAP reduces the number of extensions formed
by AsPC-1 cells. E. Numbers of extensions/μm of perimetric
distance are plotted. F. GFP-myosin IIC decorates actin filaments,
especially actin belts induced by 4-HAP in tissue spheroids. G.
Sample kymographs of line scans across active leading edges in AsPC-1 SirAct
live-stained cells. H. 4-HAP decreases retrograde flow. Medians are
plotted. Inset shows increase in bleb formation in 4-HAP-treated cells
(p=0.0028). I. AsPC-1 shCTRL and shIIA cells
show dose-dependent reduction of transwell migration upon 4-HAP treatment.
Medians are shown.