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WNT10B 在生理和疾病中的作用。

The role of WNT10B in physiology and disease.

机构信息

Department of Obstetrics and Gynecology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California at Los Angeles, USA.

出版信息

Acta Physiol (Oxf). 2012 Jan;204(1):34-51. doi: 10.1111/j.1748-1716.2011.02296.x. Epub 2011 May 7.

Abstract

Wnt10b is a member of the Wnt ligand gene family that encodes for secreted proteins, which activate the ancient and highly conserved Wnt signalling cascade. The Wnt pathway has been shown to be essential for embryonic development, tissue integrity, and stem cell activity, but if deregulated, also causes disease such as cancer. Although the 19 different Wnt ligands found in both human and mouse can activate several branches of the Wnt pathway, WNT10B specifically activates canonical Wnt/β-catenin signalling and thus triggers β-catenin/LEF/TCF-mediated transcriptional programs. In this review, we highlight the unique functions of WNT10B and mechanisms of how WNT10B acts in the immune system, mammary gland, adipose tissue, bone and skin. In these organs, WNT10B has been well established to be involved in signalling networks controlling stemness, pluripotency and cell fate decisions. Deregulation of these processes causes diseases such as breast cancer, obesity and osteoporosis. Compelling evidence suggests that WNT10B is a valuable candidate for the development of therapeutic regimens for human diseases.

摘要

Wnt10b 是 Wnt 配体基因家族的一员,其编码的分泌蛋白可激活古老且高度保守的 Wnt 信号级联反应。Wnt 通路已被证明对胚胎发育、组织完整性和干细胞活性至关重要,但如果失调,也会导致癌症等疾病。尽管在人类和小鼠中发现的 19 种不同的 Wnt 配体可以激活 Wnt 通路的几个分支,但 WNT10B 特异性激活经典的 Wnt/β-连环蛋白信号通路,从而触发β-连环蛋白/LEF/TCF 介导的转录程序。在这篇综述中,我们强调了 WNT10B 的独特功能及其在免疫系统、乳腺、脂肪组织、骨骼和皮肤中发挥作用的机制。在这些器官中,WNT10B 已被充分证明参与了控制干细胞特性、多能性和细胞命运决定的信号网络。这些过程的失调会导致乳腺癌、肥胖症和骨质疏松症等疾病。有强有力的证据表明,WNT10B 是开发人类疾病治疗方案的有价值的候选物。

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