Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer

被引：350

作者：

Wang, Yumeng ^{[1
,2
]}

Xu, Xiaoyan ^{[1
,3
]}

Maglic, Dejan ^{[4
,5
,6
]}

Dill, Michael T. ^{[4
,5
,6
]}

Mojumdar, Kamalika ^{[1
]}

Ng, Patrick Kwok-Shing ^{[7
]}

Jeong, Kang Jin ^{[8
]}

Tsang, Yiu Huen ^{[9
]}

Moreno, Daniela ^{[9
]}

Bhavana, Venkata Hemanjani ^{[9
]}

Peng, Xinxin ^{[1
]}

Ge, Zhongqi ^{[1
]}

Chen, Hu ^{[1
,2
]}

Li, Jun ^{[1
]}

Chen, Zhongyuan ^{[1
,10
]}

Zhang, Huiwen ^{[11
]}

Han, Leng ^{[11
]}

Du, Di ^{[1
]}

Creighton, Chad J. ^{[12
]}

Mills, Gordon B. ^{[8
]}

Camargo, Fernando ^{[4
,5
,6
]}

Liang, Han ^{[1
,2
,8
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[2] Baylor Coll Med, Grad Program Quantitat & Computat Biosci, Houston, TX 77030 USA

[3] China Med Univ, Dept Pathophysiol, Coll Basic Med Sci, Shenyang 110122, Liaoning, Peoples R China

[4] Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA

[5] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[6] Harvard Stem Cell Inst, Boston, MA 02115 USA

[7] Univ Texas MD Anderson Canc Ctr, Inst Personalized Canc Therapy, Houston, TX 77030 USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

[9] Baylor Coll Med, Dept Human Genet, Houston, TX 77030 USA

[10] Rice Univ, Dept Stat, Houston, TX 77005 USA

[11] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Dept Biochem & Mol Biol, Houston, TX 77030 USA

[12] Baylor Coll Med, Duncan Canc Ctr Biostat, Houston, TX 77030 USA

来源：

CELL REPORTS | 2018年 / 25卷 / 05期

基金：

瑞士国家科学基金会;

关键词：

ORGAN SIZE CONTROL; PANCREATIC-CANCER; TUMOR PROGRESSION; BREAST-CANCER; YAP; PROMOTES; TAZ; GENE; GROWTH; CELLS;

D O I：

10.1016/j.celrep.2018.10.001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional "omic'' data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era.

引用

页码：1304 / +

页数：19

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