Effects of ROCK inhibitor, Y-27632, on adhesion and mobility in esophageal squamous cell cancer cells

Abstract

Rho-associated protein kinase (ROCK), a molecular switch, modulates cellular functions in many cancers, such as hepatocellular, breast, colon cancers, etc. However, little is known the effect of ROCK on cell adhesion and mobility in esophageal squamous cell cancer (ESCC), one of the most diagnosed cancers in China. In this study, Y-27632 was used to specifically block ROCK activity in ESCC cells. Adhesion of ESCC cells was detected by homotypic and heterotypic adhesion assay together with examination of E-cadherin expression. Motility of ESCC cells changes were examined by detection of phosphorylated cofilin and observed under confocal microscopy, respectively. We found that Y-27632 increased both heterotypic and homotypic adhesion, and the expression of E-cadherin; decreased phosphorylated cofilin resulting in actin rearrangement in ESCC cells. All these findings indicate that ROCK signaling pathway plays an important role in cell adhesion and mobility, suggesting that it may be used as a potential target for therapy of ESCC.

Esophageal Epithelial Resistance and Lower Esophageal Sphincter Muscle Contraction Increase in a Chronic Diabetic Rabbit Model

“…Tight junctions are composed of the transmembrane protein occludin, junctional adhesion protein, and the claudin family, which are linked to the actin cytoskeleton via zonula occludens. Inhibition of ROCK was found to increase the adhesion and expression of e-cadherin in esophageal cancer cells, which indicates the importance of the ROCK signaling pathway in cell adhesion [22].…”

Rapid dynamics of cell-shape recovery in response to local deformations

“…In particular, increased actomyosin II assembly and activity has been observed following depletion of cofilin in HeLa cells 40 . Considering that the inhibition of ROCK with Y-27632 has been shown to increase cofilin phosphorylation in esophageal squamous cancer cells 41 , it is possible that pre-treatment here results in an accumulation of cortical F-actin. Increased phosphorylation of cofilin leads to an accumulation of actin filaments resulting in an overly contractile cortex 42 , which can account for the observed increase in resistance to deformation and slowed recovery.…”

Expression of Serum Response Factor in Gastric Carcinoma and Its Molecular Mechanisms Involved in the Regulation of the Invasion and Migration of SGC-7901 Cells

“…14,22,28,29 These reports suggest that the inhibition of Rho kinase may be one way to prevent cancer invasion and metastasis by inhibiting cell migration. 14 It has been reported that Y-27632 can increase the expression of E-cadherin and both heterotypic and homotypic adhesion.…”

“…[19][20][21] It has been shown that Y-27632 has a suppressive effect on the invasion and migration of human bladder cancer TSGH cells 14 and on the adhesion and mobility of esophageal squamous cancer cells. 22 We wanted to compare the effects of ROCK inhibition on the gastric carcinoma cells to SRF knockdown, with the expectation that ROCK inhibition with Y-27632 would inhibit the invasive properties of gastric carcinoma cells, but with relative unknown effects of cellular proliferation. To FIG.…”