Identification of c- MYC as a Target of the APC Pathway
Abstract
The adenomatous polyposis coli gene ( APC ) is a tumor suppressor gene that is inactivated in most colorectal cancers. Mutations of APC cause aberrant accumulation of β-catenin, which then binds T cell factor–4 (Tcf-4), causing increased transcriptional activation of unknown genes. Here, the c- MYC oncogene is identified as a target gene in this signaling pathway. Expression of c- MYC was shown to be repressed by wild-type APC and activated by β-catenin, and these effects were mediated through Tcf-4 binding sites in the c- MYC promoter. These results provide a molecular framework for understanding the previously enigmatic overexpression of c-MYC in colorectal cancers.
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Wnt/β-catenin signaling controls the G1/S transition.
“The Wnt/β-catenin signaling pathway is one of the mechanisms known to control G1/S transition (35–38).”
From Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade (2022) · cites this paper as [35]
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- Authors
- He, T.-C., Sparks, A. B., Rago, C., Hermeking, H., Zawel, L., da Costa, L. T., Morin, P. J., Vogelstein, B., & Kinzler, K. W.
- Affiliations
- Howard Hughes Medical Institute (US)
- T.-C. He, C. Rago, B. Vogelstein, Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA. A. B. Sparks, H. Hermeking, L. Zawel, K. W. Kinzler, Johns Hopkins Oncology Center, Baltimore, MD 21231, USA. L. T. da Costa, Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. P. J. Morin, National Institute on Aging, Baltimore, MD 21224, USA.
- Corresponding author
- Kinzler, Kenneth W.
- Venue
- Science
- Published
- 1998-09-04
- Volume
- 281
- Issue
- 5382
- Pages
- 1509-1512
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2002404925
- Cited by
- 4,566
- References
- 1
- Citations by year
- 2026: 41 · 2025: 55 · 2024: 75 · 2023: 70 · 2022: 87 · 2021: 138 · 2020: 122 · 2019: 126 · 2018: 116 · 2017: 157 · 2016: 160 · 2015: 176 · 2014: 210 · 2013: 204 · 2012: 189
- FWCI
- 64.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 57345, P50CA062924, CA 62924)
- National Institute of General Medical Sciences (T32GM007309, GM07309)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- c-Myc, APC gene, β-catenin, TCF4, Wnt signaling, colorectal cancer, tumor suppressor, transcriptional regulation, c-myc promoter, oncogene overexpression
- MeSH terms
- Binding Sites, Cell Line, Cytoskeletal Proteins, Humans, Mutation, Promoter Regions, Genetic, Transcription Factors, Transcription, Genetic, Colorectal Neoplasms, Signal Transduction, Trans-Activators, Gene Expression Regulation, Neoplastic, Genes, myc, Proto-Oncogene Proteins c-myc, Genes, APC, Genes, Reporter, HT29 Cells, Adenomatous Polyposis Coli Protein, beta Catenin, TCF Transcription Factors, Transcription Factor 7-Like 2 Protein
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