Molecular Mechanisms of Cancer Program, Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca, 37007, Salamanca, Spain.
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, 37007, Salamanca, Spain.
Oncogene. 2022 Jun;41(24):3341-3354. doi: 10.1038/s41388-022-02341-7. Epub 2022 May 9.
It is known that Rho GTPases control different aspects of the biology of skin stem cells (SSCs). However, little information is available on the role of their upstream regulators under normal and tumorigenic conditions in this process. To address this issue, we have used here mouse models in which the activity of guanosine nucleotide exchange factors of the Vav subfamily has been manipulated using both gain- and loss-of-function strategies. These experiments indicate that Vav2 and Vav3 regulate the number, functional status, and responsiveness of hair follicle bulge stem cells. This is linked to gene expression programs related to the reinforcement of the identity and the quiescent state of normal SSCs. By contrast, in the case of cancer stem cells, they promote transcriptomal programs associated with the identity, activation state, and cytoskeletal remodeling. These results underscore the role of these Rho exchange factors in the regulation of normal and tumor epidermal stem cells.
已知 Rho GTPases 控制皮肤干细胞（SSC）生物学的不同方面。然而，在这个过程中，关于它们在正常和肿瘤发生条件下的上游调节剂的作用的信息很少。为了解决这个问题，我们在这里使用了小鼠模型，使用功能获得和功能丧失策略来操纵 Vav 亚家族鸟嘌呤核苷酸交换因子的活性。这些实验表明，Vav2 和 Vav3 调节毛囊隆突干细胞的数量、功能状态和反应性。这与与正常 SSC 的身份和静止状态的强化相关的基因表达程序有关。相比之下，在癌症干细胞的情况下，它们促进与身份、激活状态和细胞骨架重塑相关的转录组程序。这些结果强调了这些 Rho 交换因子在调节正常和肿瘤表皮干细胞中的作用。
