2019
DOI: 10.1016/j.actbio.2019.02.015
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ROCK isoforms differentially modulate cancer cell motility by mechanosensing the substrate stiffness

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Cited by 102 publications
(66 citation statements)
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References 60 publications
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“…On the other hand, results suggest that the stiffness regulates in a similar way TER and that the stiffening of the tumor ECM increases the directionality of cell trajectory independently from cell type and, consequently, cell velocity. This result also gives more insights about previous findings on persistence time [29] and supports previous observation demonstrating that stiff substrates promote directional migration [43]. In particular, it has been demonstrated that substrate stiffness regulates RhoA/ROCK1/p-MLC and RhoA/ROCK2/pcofilin pathways, strongly implicated in the progression and metastasis of many cancers included breast cancer, through the activation of integrin β1 and FAK [44][45][46].…”
Section: Discussionsupporting
confidence: 89%
“…On the other hand, results suggest that the stiffness regulates in a similar way TER and that the stiffening of the tumor ECM increases the directionality of cell trajectory independently from cell type and, consequently, cell velocity. This result also gives more insights about previous findings on persistence time [29] and supports previous observation demonstrating that stiff substrates promote directional migration [43]. In particular, it has been demonstrated that substrate stiffness regulates RhoA/ROCK1/p-MLC and RhoA/ROCK2/pcofilin pathways, strongly implicated in the progression and metastasis of many cancers included breast cancer, through the activation of integrin β1 and FAK [44][45][46].…”
Section: Discussionsupporting
confidence: 89%
“…Experiments confirmed that ROCK1, but not ROCK2, acted on the phosphorylation of myosin regulatory light chain, and ROCK2 acted more on the phosphorylation of Cofilin. 40 Cofilin is a low molecular-weight actin-modulating protein, which can inhibit its binding to actin after binding with inositol triphosphate (IP). Ample evidence show that a chemokine receptor activates Phospholipases C, catalyzes decomposition of PIP2 (PIP, hosphatidylinositol biphosphate), produces IP3, binds IP3 receptor, and releases intracellular Ca 2þ from endoplasmic reticulum.…”
Section: Discussionmentioning
confidence: 99%
“…RHOA subsequently activates diaphanous 1 (DIA1) and RHO-associated coiled-coil-containing protein kinase (ROCK) [ 195 ]. Then, JNK activates CapZ-interacting protein (CapZIP) [ 196 ], ROCK activates mitogen-activated protein kinase (MRLC) [ 197 ], and DAAM activates Profilin [ 198 ]. These PCP effectors lead to the development of lateral asymmetry in epithelial sheets and other structures [ 199 ], as well as cell polarity and migration by remodeling the cytoskeleton [ 200 ] (Fig.…”
Section: Introductionmentioning
confidence: 99%