Ding Mei, Wang Xin
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Oncol Lett. 2017 Dec;14(6):6327-6333. doi: 10.3892/ol.2017.7030. Epub 2017 Sep 22.
The crosstalk of multiple cellular signaling pathways is crucial in animal development and tissue homeostasis, and its dysregulation may result in tumor formation and metastasis. The Hedgehog (Hh) and Wnt signaling pathways are both considered to be essential regulators of cell proliferation, differentiation and oncogenesis. Recent studies have indicated that the Hh and Wnt signaling pathways are closely associated and involved in regulating embryogenesis and cellular differentiation. Hh signaling acts upstream of the Wnt signaling pathway, and negative regulates Wnt activity via secreted frizzled-related protein 1 (SFRP1), and the Wnt/β-catenin pathway downregulates Hh activity through glioma-associated oncogene homolog 3 transcriptional regulation. This evidence suggests that the imbalance of Hh and Wnt regulation serves a crucial role in cancer-associated processes. The activation of SFRP1, which inhibits Wnt, has been demonstrated to be an important cross-point between the two signaling pathways. The present study reviews the complex interaction between the Hh and Wnt signaling pathways in embryogenesis and tumorigenicity, and the role of SFRP1 as an important mediator associated with the dysregulation of the Hh and Wnt signaling pathways.
多种细胞信号通路的相互作用在动物发育和组织稳态中至关重要，其失调可能导致肿瘤形成和转移。刺猬信号通路（Hh）和Wnt信号通路均被认为是细胞增殖、分化和肿瘤发生的重要调节因子。最近的研究表明，Hh信号通路和Wnt信号通路密切相关，并参与调节胚胎发育和细胞分化。Hh信号通路在Wnt信号通路的上游起作用，并通过分泌型卷曲相关蛋白1（SFRP1）负向调节Wnt活性，而Wnt/β-连环蛋白通路则通过胶质瘤相关癌基因同源物3转录调控下调Hh活性。这一证据表明，Hh和Wnt调节的失衡在癌症相关过程中起着关键作用。已证明抑制Wnt的SFRP1的激活是这两条信号通路之间的一个重要交叉点。本研究综述了Hh信号通路和Wnt信号通路在胚胎发育和肿瘤发生中的复杂相互作用，以及SFRP1作为与Hh和Wnt信号通路失调相关的重要介质的作用。
