Kim Jee-Heun, Park So-Yeon, Jun Youngsoo, Kim Ji-Young, Nam Jeong-Seok
School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Korea.
Cell Logistics Research Center, Gwangju Institute of Science and Technology, Gwangju 61005, Korea.
Int J Mol Sci. 2017 Jul 25;18(8):1604. doi: 10.3390/ijms18081604.
The importance of Wnt/β-catenin signaling in cancer stem cells (CSCs) has been acknowledged; however, the mechanism through which it regulates the biological function of CSCs and promotes cancer progression remains elusive. Hence, to understand the intricate mechanism by which Wnt controls stemness, the specific downstream target genes of Wnt were established by analyzing the genetic signatures of multiple types of metastatic cancers based on gene set enrichment. By focusing on the molecular function of Wnt target genes, the biological roles of Wnt were interpreted in terms of CSC dynamics from initiation to metastasis. Wnt signaling participates in cancer initiation by generating CSCs from normal stem cells or non-CSCs and augmenting persistent growth at the primary region, which is resistant to anti-cancer therapy. Moreover, it assists CSCs in invading nearby tissues and in entering the blood stream, during which the negative feedback of the Wnt signaling pathway maintains CSCs in a dormant state that is suitable for survival. When CSCs arrive at distant organs, another burst of Wnt signaling induces CSCs to succeed in re-initiation and colonization. This comprehensive understanding of Wnt target genes provides a plausible explanation for how Wnt allows CSCs variation during cancer progression.
Wnt/β-连环蛋白信号通路在癌症干细胞（CSCs）中的重要性已得到认可；然而，其调节CSCs生物学功能并促进癌症进展的机制仍不清楚。因此，为了理解Wnt控制干性的复杂机制，通过基于基因集富集分析多种转移性癌症的基因特征，确定了Wnt的特定下游靶基因。通过关注Wnt靶基因的分子功能，从CSC从起始到转移的动态变化角度解释了Wnt的生物学作用。Wnt信号通路通过从正常干细胞或非CSCs产生CSCs并增强原发部位的持续生长来参与癌症起始，而原发部位的生长对抗癌治疗具有抗性。此外，它帮助CSCs侵入附近组织并进入血流，在此过程中Wnt信号通路的负反馈使CSCs维持在适合生存的休眠状态。当CSCs到达远处器官时，另一波Wnt信号诱导CSCs成功重新起始和定植。对Wnt靶基因的这种全面理解为Wnt如何在癌症进展过程中使CSCs发生变化提供了一个合理的解释。
