TGIF在致癌性Wnt信号传导中的作用。

TGIF function in oncogenic Wnt signaling.

作者信息

Razzaque Mohammed S, Atfi Azeddine

机构信息

Department of Applied Oral Sciences, The Forsyth Institute, Harvard School of Dental Medicine Affiliate, 245 First Street, Cambridge, MA 02142, USA; Department of Pathology, Saba University School of Medicine, Church Street, Saba, Dutch Caribbean.

Cancer Institute and Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA; INSERM UMRS 938, Laboratory of Cell Signaling and Carcinogenesis, Hôpital Saint-Antoine, 34 rue Crozatier, 75012 Paris, France.

出版信息

Biochim Biophys Acta. 2016 Apr;1865(2):101-4. doi: 10.1016/j.bbcan.2015.10.003. Epub 2015 Nov 11.

DOI:10.1016/j.bbcan.2015.10.003

PMID:26522669

Abstract

Transforming growth-interacting factor (TGIF) has been implicated in the pathogenesis of many types of human cancer, but the underlying mechanisms remained mostly enigmatic. Our recent study has revealed that TGIF functions as a mediator of oncogenic Wnt/β-catenin signaling. We found that TGIF can interact with and sequesters Axin1 and Axin2 into the nucleus, thereby culminating in disassembly of the β-catenin-destruction complex and attendant accumulation of β-catenin in the nucleus, where it activates expression of Wnt target genes, including TGIF itself. We have provided proof-of-concept evidences that high levels of TGIF expression correlate with poor prognosis in patients with triple negative breast cancer (TNBC), and that TGIF empowers Wnt-driven mammary tumorigenesis in vivo. Here, we will briefly summarize how TGIF influences Wnt signaling to promote tumorigenesis.

摘要

转化生长相互作用因子（TGIF）与多种人类癌症的发病机制有关，但其潜在机制大多仍不清楚。我们最近的研究表明，TGIF作为致癌性Wnt/β-连环蛋白信号传导的介质发挥作用。我们发现TGIF可以与Axin1和Axin2相互作用并将它们隔离到细胞核中，从而导致β-连环蛋白破坏复合物的解体以及随之而来的β-连环蛋白在细胞核中的积累，在细胞核中它激活Wnt靶基因的表达，包括TGIF自身。我们已经提供了概念验证证据，表明TGIF的高表达与三阴性乳腺癌（TNBC）患者的不良预后相关，并且TGIF在体内增强了Wnt驱动的乳腺肿瘤发生。在这里，我们将简要总结TGIF如何影响Wnt信号传导以促进肿瘤发生。