Targeting YAP and Hippo signaling pathway in liver cancer

被引:95
作者
Liu, Angela M. [2 ,3 ]
Xu, Michelle Z. [1 ]
Chen, Jinfei [1 ]
Poon, Ronnie T. [3 ]
Luk, John M. [2 ,4 ,5 ]
机构
[1] Nanjing Med Univ, Affiliated Nanjing Hosp 1, Dept Oncol, Nanjing 21006, Peoples R China
[2] Natl Univ Singapore MD11, Dept Pharmacol, Singapore 117597, Singapore
[3] Univ Hong Kong, Dept Surg, Pokfulam, Hong Kong, Peoples R China
[4] Natl Univ Singapore, Dept Surg, Singapore 117597, Singapore
[5] Natl Univ Singapore, Canc Sci Inst, Singapore 117597, Singapore
关键词
Hippo pathway; liver cancer; molecular therapeutics; YAP oncogene; YES-ASSOCIATED PROTEIN; TUMOR-SUPPRESSOR GENE; TISSUE-GROWTH-FACTOR; REGULATE CELL-PROLIFERATION; WW DOMAIN; DOWN-REGULATION; ORGAN SIZE; PROMOTER HYPERMETHYLATION; ANTISENSE OLIGONUCLEOTIDE; DROSOPHILA-MELANOGASTER;
D O I
10.1517/14728222.2010.499361
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Importance of the field: The Hippo signaling pathway plays pivotal roles in controlling both cell growth and organ size, emerging as a new paradigm in tumor suppression. Yes-associated protein (YAP) functions as a potent transcription co-activator and is a major downstream target tightly regulated by the Hippo pathway. Inactivation of the Hippo signaling induces YAP-mediated activation of various target genes that functionally causes cellular proliferation and outgrowth of organ size. Recently, YAP has been implicated as a bona fide oncogene in solid tumors, but little is known about its exact molecular mechanism in carcinogenesis. Areas covered in this review: We discuss the latest important findings in the Hippo signaling pathway and the possible means of developing potential cancer therapeutics by targeting multiple sites along the Hippo pathway. What the reader will gain: An overview of the emerging roles of YAP and Hippo signaling in oncogenesis and the possible ways of developing cancer therapies against the pathway components, downstream targets or interconnected pathways. Take home message: YAP is a key oncogenic driver in liver carcinogenesis and deregulation of the Hippo pathway causes tumor formation and malignancy. Targeting YAP and cognate downstream signaling targets may have clinical utility in cancer therapies.
引用
收藏
页码:855 / 868
页数:14
相关论文
共 50 条
[21]   Targeting the Hippo/YAP1 signaling pathway in hepatocellular carcinoma: From mechanisms to therapeutic drugs (Review) [J].
Li, Shenghao ;
Hao, Liyuan ;
Li, Na ;
Hu, Xiaoyu ;
Yan, Huimin ;
Dai, Erhei ;
Shi, Xinli .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2024, 65 (03)
[22]   The Hippo Signaling Pathway in Development and Cancer [J].
Pan, Duojia .
DEVELOPMENTAL CELL, 2010, 19 (04) :491-505
[23]   The Hippo Signaling Pathway in Cancer: A Cell Cycle Perspective [J].
Xiao, Yi ;
Dong, Jixin .
CANCERS, 2021, 13 (24)
[24]   Control of Proliferation and Cancer Growth by the Hippo Signaling Pathway [J].
Ehmer, Ursula ;
Sage, Julien .
MOLECULAR CANCER RESEARCH, 2016, 14 (02) :127-140
[25]   The regulatory networks of the Hippo signaling pathway in cancer development [J].
Wang, Maonan ;
Dai, Manli ;
Wang, Dan ;
Xiong, Wei ;
Zeng, Zhaoyang ;
Guo, Can .
JOURNAL OF CANCER, 2021, 12 (20) :6216-6230
[26]   The Hippo signaling pathway in stem cell biology and cancer [J].
Mo, Jung-Soon ;
Park, Hyun Woo ;
Guan, Kun-Liang .
EMBO REPORTS, 2014, 15 (06) :642-656
[27]   The Hippo Pathway and YAP Signaling: Emerging Concepts in Regulation, Signaling, and Experimental Targeting Strategies With Implications for Hepatobiliary Malignancies [J].
Werneburg, Nathan ;
Gores, Gregory J. ;
Smoot, Rory L. .
GENE EXPRESSION-THE JOURNAL OF LIVER RESEARCH, 2020, 20 (01) :67-74
[28]   Linking Extracellular Matrix Agrin to the Hippo Pathway in Liver Cancer and Beyond [J].
Chakraborty, Sayan ;
Hong, Wanjin .
CANCERS, 2018, 10 (02)
[29]   The Hippo Pathway in Biological Control and Cancer Development [J].
Chan, Siew Wee ;
Lim, Chun Jye ;
Chen, Liming ;
Chong, Yaan Fun ;
Huang, Caixia ;
Song, Haiwei ;
Hong, Wanjin .
JOURNAL OF CELLULAR PHYSIOLOGY, 2011, 226 (04) :928-939
[30]   The Hippo Pathway in Liver Homeostasis and Pathophysiology [J].
Driskill, Jordan H. ;
Pan, Duojia .
ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 16, 2021, 2021, 16 :299-322