Hippo信号通路在乳腺癌中的调控机制及作用

doi:10.16288/j.yczz.17-100

遗传 ›› 2017, Vol. 39 ›› Issue (7): 617-629.doi: 10.16288/j.yczz.17-100

Hippo信号通路在乳腺癌中的调控机制及作用

姚传波¹(),周鑫²(),陈策实³,雷群英¹()

1. 复旦大学附属肿瘤医院肿瘤研究所,生物医学研究院肿瘤代谢实验室,上海 200032
2. 德克萨斯大学MD安德森癌症中心肿瘤生物学系,休斯顿 77030
3. 中国科学院昆明动物研究所肿瘤生物学实验室,昆明 650223

收稿日期:2017-03-23 修回日期:2017-04-14 出版日期:2017-07-20 发布日期:2017-06-08
作者简介:姚传波,硕士研究生,专业方向：肿瘤代谢。E-mail: 14211010030@fudan.edu.cn|周鑫,博士,研究方向：Hippo信号通路与肿瘤。E-mail: XZhou8@mdanderson.org|雷群英,教授,博士生导师,研究方向：肿瘤代谢。E-mail: qlei@fudan.edu.cn
基金资助:
国家重点基础研究发展规划(973计划)项目(2015CB910401);国家自然科学基金项目(81430057,81572686)

The regulatory mechanisms and functional roles of the Hippo signaling pathway in breast cancer

Chuanbo Yao¹(),Xin Zhou²(),Ceshi Chen³,Qunying Lei¹(),

1. Cancer Institute, Fudan University Shanghai Cancer Center and Cancer Metabolism Laboratory of Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
2. Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston 77030, USA
3. Laboratory of Cancer Biology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China

Received:2017-03-23 Revised:2017-04-14 Published:2017-07-20 Online:2017-06-08
Supported by:
the National Basic Research Program of China (973 Program)(2015CB910401);the National Natural Science Foundation of China(81430057,81572686)

摘要/Abstract

摘要：

Hippo信号通路是调控器官大小和肿瘤发生发展的关键通路,近年来受到广泛的关注。TAZ/YAP作为哺乳动物中Hippo信号通路两个核心下游效应分子,通过Hippo信号通路依赖性和非依赖性的机制受到细胞内外信号的严密调控。除了参与正常乳腺组织发育,Hippo信号通路还在人乳腺癌细胞的增殖、分化、凋亡、迁移、侵袭、上皮-间质转化和干性维持等多个过程中起着关键性作用。本文总结了Hippo信号通路的调控机制和调节信号,阐述了Hippo信号通路异常在乳腺癌发生发展中的作用,并讨论了其在乳腺癌中作为治疗靶点的临床策略。

关键词: TAZ/YAP, Hippo信号通路, 乳腺癌

Abstract:

Hippo signaling pathway has attracted broad attention due to its essential roles in controlling organ size and tumorigenesis. TAZ/YAP, two core downstream molecules of the Hippo signaling pathway in mammals, are tightly regulated by a wide range of extracellular and intrinsic signals in both Hippo signaling pathway-dependent and -independent manners. Besides their roles in the development and function of normal mammary glands, TAZ/YAP display remarkable potency and relevance to multiple aspects of human breast carcinogenesis, including cellular proliferation, differentiation, apoptosis, migration, invasion, epithelial-mesenchymal transition and stemness. In this review, we summarize the regulators of TAZ/YAP, discuss the significant contribution of the Hippo signaling pathway to human breast cancers and highlight their potential therapeutic roles.

Key words: TAZ/YAP, Hippo signaling pathway, breast cancer

姚传波, 周鑫, 陈策实, 雷群英. Hippo信号通路在乳腺癌中的调控机制及作用[J]. 遗传, 2017, 39(7): 617-629.

Chuanbo Yao, Xin Zhou, Ceshi Chen, Qunying Lei, . The regulatory mechanisms and functional roles of the Hippo signaling pathway in breast cancer[J]. Hereditas(Beijing), 2017, 39(7): 617-629.

参考文献

[1]	Siegel R, Ma JM, Zou ZH, Jemal A. Cancer statistics, 2014. CA Cancer J Clin, 2014, 64(1): 9-29.
[2]	Perou CM, S?rlie T, Eisen MB, Van De Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge ?, Pergamenschikov A, Williams C, Zhu SX, L?nning PE, B?rresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumours. Nature, 2000, 406(6797): 747-752.
[3]	The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature, 2012, 490(7418): 61-70.
[4]	Johnson R, Halder G. The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment. Nat Rev Drug Discov, 2014, 13(1): 63-79.
[5]	Zhao B, Wei XM, Li WQ, Udan RS, Yang Q, Kim J, Xie J, Ikenoue T, Yu JD, Li L, Zheng P, Ye KQ, Chinnaiyan A, Halder G, Lai ZC, Guan KL. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev, 2007, 21(21): 2747-2761.
[6]	Lei QY, Zhang H, Zhao B, Zha ZY, Bai F, Pei XH, Zhao SM, Xiong Y, Guan KL. TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway. Mol Cell Biol, 2008, 28(7): 2426-2436.
[7]	Cui CB, Cooper LF, Yang XL, Karsenty G, Aukhil I. Transcriptional coactivation of bone-specific transcription factor Cbfa1 by TAZ. Mol Cell Biol, 2003, 23(3): 1004-1013.
[8]	Jeong H, Bae S, An SY, Byun MR, Hwang JH, Yaffe MB, Hong JH, Hwang ES. TAZ as a novel enhancer of MyoD-mediated myogenic differentiation. FASEB J, 2010, 24(9): 3310-3320.
[9]	Hong JH, Hwang ES, McManus MT, Amsterdam A, Tian Y, Kalmukova R, Mueller E, Benjamin T, Spiegelman BM, Sharp PA, Hopkins N, Yaffe MB. TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science, 2005, 309(5737): 1074-1078.
[10]	Park KS, Whitsett JA, Di Palma T, Hong JH, Yaffe MB, Zannini M. TAZ interacts with TTF-1 and regulates expression of surfactant protein-C. J Biol Chem, 2004, 279(17): 17384-17390.
[11]	Murakami M, Tominaga J, Makita R, Uchijima Y, Kurihara Y, Nakagawa O, Asano T, Kurihara H. Transcriptional activity of Pax3 is co-activated by TAZ. Biochem Biophys Res Commun, 2006, 339(2): 533-539.
[12]	Di Palma T, D'Andrea B, Liguori GL, Liguoro A, de Cristofaro T, Del Prete D, Pappalardo A, Mascia A, Zannini M. TAZ is a coactivator for Pax8 and TTF-1, two transcription factors involved in thyroid differentiation. Exp Cell Res, 2009, 315(2): 162-175.
[13]	Varelas X, Sakuma R, Samavarchi-Tehrani P, Peerani R, Rao BM, Dembowy J, Yaffe MB, Zandstra PW, Wrana JL. TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal. Nat Cell Biol, 2008, 10(7): 837-848.

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

Hippo信号通路在乳腺癌中的调控机制及作用

The regulatory mechanisms and functional roles of the Hippo signaling pathway in breast cancer

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics