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Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer.

Publication ,  Journal Article
Wang, Y; Xu, X; Maglic, D; Dill, MT; Mojumdar, K; Ng, PK-S; Jeong, KJ; Tsang, YH; Moreno, D; Bhavana, VH; Peng, X; Ge, Z; Chen, H; Li, J ...
Published in: Cell Rep
October 30, 2018
Published version (DOI) Link to item

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.

Duke Scholars

Quinn Ostrom
Author Quinn Ostrom Neurosurgery, Neuro-Oncology
Andrew Berchuck
Author Andrew Berchuck Obstetrics and Gynecology, Gynecologic Oncology
Jeffrey R. Marks
Author Jeffrey R. Marks Surgery, Surgical Sciences
Shannon Jones McCall
Author Shannon Jones McCall Pathology
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Published In

Cell Rep

DOI

10.1016/j.celrep.2018.10.001

EISSN

2211-1247

Publication Date

October 30, 2018

Volume

25

Issue

5

Start / End Page

1304 / 1317.e5

Location

United States

Related Subject Headings

  • Signal Transduction
  • Protein Serine-Threonine Kinases
  • Prognosis
  • Neoplasms
  • Mutation
  • Models, Biological
  • MicroRNAs
  • Humans
  • Hippo Signaling Pathway
  • Gene Expression Regulation, Neoplastic
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, Y., Xu, X., Maglic, D., Dill, M. T., Mojumdar, K., Ng, P.-S., … Liang, H. (2018). Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer. Cell Rep, 25(5), 1304-1317.e5. https://doi.org/10.1016/j.celrep.2018.10.001
Wang, Yumeng, Xiaoyan Xu, Dejan Maglic, Michael T. Dill, Kamalika Mojumdar, Patrick Kwok-Shing Ng, Kang Jin Jeong, et al. “Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer.” Cell Rep 25, no. 5 (October 30, 2018): 1304-1317.e5. https://doi.org/10.1016/j.celrep.2018.10.001.
Wang Y, Xu X, Maglic D, Dill MT, Mojumdar K, Ng PK-S, et al. Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer. Cell Rep. 2018 Oct 30;25(5):1304-1317.e5.
Wang, Yumeng, et al. “Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer.” Cell Rep, vol. 25, no. 5, Oct. 2018, pp. 1304-1317.e5. Pubmed, doi:10.1016/j.celrep.2018.10.001.
Wang Y, Xu X, Maglic D, Dill MT, Mojumdar K, Ng PK-S, Jeong KJ, Tsang YH, Moreno D, Bhavana VH, Peng X, Ge Z, Chen H, Li J, Chen Z, Zhang H, Han L, Du D, Creighton CJ, Mills GB, Cancer Genome Atlas Research Network, Camargo F, Liang H. Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer. Cell Rep. 2018 Oct 30;25(5):1304-1317.e5.
Journal cover image

Published In

Cell Rep

DOI

10.1016/j.celrep.2018.10.001

EISSN

2211-1247

Publication Date

October 30, 2018

Volume

25

Issue

5

Start / End Page

1304 / 1317.e5

Location

United States

Related Subject Headings

  • Signal Transduction
  • Protein Serine-Threonine Kinases
  • Prognosis
  • Neoplasms
  • Mutation
  • Models, Biological
  • MicroRNAs
  • Humans
  • Hippo Signaling Pathway
  • Gene Expression Regulation, Neoplastic