肺上皮发育依赖于细胞增殖和分化的适当平衡来维持稳态。当这种平衡被打破时,它会导致癌症等疾病,其中细胞经历过度增殖,然后可以进行迁移和转移。肺癌是最致命的癌症之一,尽管有各种各样的治疗方法,有些情况下治疗仍然难以捉摸。由于rho相关蛋白激酶(ROCK)在激活致癌信号通路中的作用,因此被认为是理想的分子靶标。然而,在各种情况下,已证明对ROCK的抑制具有相反的结果。这里,我们表明,用Y-27632抑制ROCK导致非洲爪狼胚胎皮肤上皮组织发育异常,这是研究肺癌发展的理想模型。我们发现,用y-27632处理会导致增殖增加,并沿尾部边缘形成纤毛上皮外生长物。我们的研究结果表明,在某些情况下,ROCK抑制可以扰乱组织稳态。我们预计这些发现可以提供对克服ROCK抑制导致增殖增加的情况的可能机制的见解。此外,这些发现是重要的,因为y-27632是用于研究ROCK信号传导的常见药理学抑制剂,所以重要的是要知道,在某些体内发育模型和条件下,这种治疗可以增强增殖,而不是导致细胞周期抑制。
Lung epithelial development relies on the proper balance of cell proliferation and differentiation to maintain homeostasis. When this balance is disturbed, it can lead to diseases like cancer, where cells undergo hyperproliferation and then can undergo migration and metastasis. Lung cancer is one of the deadliest cancers, and even though there are a variety of therapeutic approaches, there are cases where treatment remains elusive. The rho-associated protein kinase (
ROCK) has been thought to be an ideal molecular target due to its role in activating oncogenic signaling pathways. However, in a variety of cases, inhibition of
ROCK has been shown to have the opposite outcome. Here, we show that
ROCK inhibition with y-27632 causes abnormal epithelial tissue development in Xenopus laevis embryonic skin, which is an ideal model for studying lung cancer development. We found that treatment with y-27632 caused an increase in proliferation and the formation of ciliated epithelial outgrowths along the tail edge. Our results suggest that, in certain cases,
ROCK inhibition can disturb tissue homeostasis. We anticipate that these findings could provide insight into possible mechanisms to overcome instances when ROCK inhibition results in heightened proliferation. Also, these findings are significant because y-27632 is a common pharmacological inhibitor used to study
ROCK signaling, so it is important to know that in certain in vivo developmental models and conditions, this treatment can enhance proliferation rather than lead to cell cycle suppression.