Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach
Open accessAbstract
The heterogeneity and instability of human tumors hamper straightforward identification of cancer-causing mutations through genomic approaches alone. Herein we describe a mouse model of liver cancer initiated from progenitor cells harboring defined cancer-predisposing lesions. Genome-wide analyses of tumors in this mouse model and in human hepatocellular carcinomas revealed a recurrent amplification at mouse chromosome 9qA1, the syntenic region of human chromosome 11q22. Gene-expression analyses delineated cIAP1, a known inhibitor of apoptosis, and Yap, a transcription factor, as candidate oncogenes in the amplicon. In the genetic context of their amplification, both cIAP1 and Yap accelerated tumorigenesis and were required to sustain rapid growth of amplicon-containing tumors. Furthermore, cIAP1 and Yap cooperated to promote tumorigenesis. Our results establish a tractable model of liver cancer, identify two oncogenes that cooperate by virtue of their coamplification in the same genomic locus, and suggest an efficient strategy for the annotation of human cancer genes.
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The Hippo pathway controls liver size and is commonly amplified in human hepatocellular carcinoma.
“This pathway controls liver size and is commonly amplified in human hepatocellular carcinoma (Camargo et al., 2007; Zender et al., 2006).”
From Hippo Signaling Influences HNF4A and FOXA2 Enhancer Switching during Hepatocyte Differentiation (2014) · cites this paper as Zender et al., 2006
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- Authors
- Zender, L., Spector, M. S., Xue, W., Flemming, P., Cordon-Cardo, C., Silke, J., Fan, S.-T., Luk, J. M., Wigler, M., Hannon, G. J., Mu, D., Lucito, R., Powers, S., & Lowe, S. W.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- Medizinische Hochschule Hannover (DE)
- Walter and Eliza Hall Institute of Medical Research (AU)
- University of Hong Kong (HK)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Lowe, Scott W.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 125
- Issue
- 7
- Pages
- 1253-1267
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3026384
- OpenAlex
- W2101538557
- Cited by
- 1,065
- References
- 5
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 24 · 2023: 29 · 2022: 42 · 2021: 43 · 2020: 31 · 2019: 36 · 2018: 64 · 2017: 67 · 2016: 62 · 2015: 68 · 2014: 91 · 2013: 79 · 2012: 80
- FWCI
- 23.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2603 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (CA105388, CA13106, CA-87497, U01CA105388, P01CA087497, R01CA078544, P01CA013106, P30CA008748, CA078544)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- liver cancer, hepatocellular carcinoma, oncogenes, cIAP1, YAP, 11Q22, mouse model, liver progenitor cells, cancer susceptibility, carcinogenesis, oncogene cooperation
- MeSH terms
- YAP-Signaling Proteins, Animals, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Liver Neoplasms, Experimental, Mutation, Nuclear Proteins, Oncogenes, Phosphoproteins, Species Specificity, Transcription Factors, Trans-Activators, Genes, p53, Mice, Knockout, Cell Cycle Proteins, Oligonucleotide Array Sequence Analysis, Genomics, Adaptor Proteins, Signal Transducing, Inhibitor of Apoptosis Proteins, Mice
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