Jerrell Rachel J, Leih Mitchell J, Parekh Aron
Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, TN, USA.
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Small GTPases. 2020 Mar;11(2):131-137. doi: 10.1080/21541248.2017.1341366. Epub 2017 Sep 18.
Rho-associated kinase (ROCK) activity drives cell migration via actomyosin contractility. During invasion, individual cancer cells can transition between 2 modes of migration, mesenchymal and amoeboid. Changes in ROCK activity can cause a switch between these migration phenotypes which are defined by distinct morphologies. However, recent studies have shown that the ROCK isoforms are not functionally redundant as previously thought. Therefore, it is unclear whether the ROCK isoforms play different roles in regulating migration phenotypes. Here, we found that ROCK1 and ROCK2 differentially regulate carcinoma cell morphology resulting in intermediate phenotypes that share some mesenchymal and amoeboid characteristics. These findings suggest that the ROCK isoforms play unique roles in the phenotypic plasticity of mesenchymal carcinoma cells which may have therapeutic implications.
Rho相关激酶(ROCK)活性通过肌动球蛋白收缩性驱动细胞迁移。在侵袭过程中,单个癌细胞可在间充质和阿米巴样两种迁移模式之间转变。ROCK活性的变化可导致由不同形态定义的这些迁移表型之间的转换。然而,最近的研究表明,ROCK同工型并不像以前认为的那样在功能上是冗余的。因此,尚不清楚ROCK同工型在调节迁移表型中是否发挥不同作用。在此,我们发现ROCK1和ROCK2对癌细胞形态的调节存在差异,导致出现兼具一些间充质和阿米巴样特征的中间表型。这些发现表明,ROCK同工型在间充质癌细胞的表型可塑性中发挥独特作用,这可能具有治疗意义。