Figure 9

A mechanotransduction pathway comprising ROCK, actomyosin contractility, and FAK controls disaggregation of ovarian cancer spheroids. (A) Traction forces underlying SKOV3 ovarian cancer spheroids at 2 h after plating on FN-coated hydrogels with rigidities of 3 kPa, 25 kPa, or 125 kPa, as indicated. Phase contrast images (top), calculated traction forces with local scaling (middle), and calculated traction forces with global scaling (bottom) are shown for representative spheroids on each hydrogel rigidity. (B) Phase contrast images of SKOV3 ovarian cancer spheroids, treated 2 h after plating with 0.1% DMSO (Ctrl), 25 µM blebbistatin, 10 µM fasudil, and 0.25 µM PF271, were captured at 4 h and 20 h post plating on hydrogels with rigidity of 25 kPa. Red lines help visualize the boundaries of the tumor spheroids at each timepoint. (C) Quantification of changes in area between 2 hours and 20 hours of DMSO control-, blebbistatin-, fasudil-, and PF271-treated spheroids (n = 16 spheroids for each treatment; *p = 0.0286; ***p < 0.001).