Kahn Michael
Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California.
Semin Reprod Med. 2015 Sep;33(5):317-25. doi: 10.1055/s-0035-1558404. Epub 2015 Aug 6.
The Wnt signaling cascade is critically important in stem cell biology, both in homeostatic maintenance and repair and regeneration of tissues and organs, through their respective somatic stem cells (SSCs). However, aberrant Wnt signaling is associated with a wide array of tumor types and Wnt signaling is important in the so-termed cancer stem cell/tumor-initiating cell (CSC/TIC) population. The ability to safely therapeutically target the Wnt signaling pathway offers enormous promise. However, just like the Sword of Damocles, significant risks and concerns regarding targeting such a critical pathway in normal stem cell maintenance and tissue homeostasis remain ever present. With this in mind, we review our current understanding of the role of Wnt signaling in SSCs and CSC/TICs and the potential to pharmacologically manipulate these endogenous stem cell populations (both normal and tumor).
Wnt信号级联在干细胞生物学中至关重要,在组织和器官的稳态维持、修复及再生过程中,通过各自的体干细胞(SSCs)发挥作用。然而,异常的Wnt信号与多种肿瘤类型相关,并且Wnt信号在所谓的癌症干细胞/肿瘤起始细胞(CSC/TIC)群体中也很重要。安全地对Wnt信号通路进行治疗性靶向具有巨大的前景。然而,就像达摩克利斯之剑一样,针对正常干细胞维持和组织稳态中的如此关键的通路进行靶向,仍然存在重大风险和问题。考虑到这一点,我们综述了目前对Wnt信号在体干细胞以及癌症干细胞/肿瘤起始细胞中的作用的理解,以及对这些内源性干细胞群体(包括正常和肿瘤干细胞)进行药理学操控的潜力。