ArticleGastroenterology2008
The APC tumor suppressor inhibits DNA replication by directly binding to DNA via its carboxyl terminus.
Article in Gastroenterology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Circulating tumor DNA methylation markers for the early diagnosis of hepatocellular carcinoma.Clinical and experimental medicine · 2025Article
- Role of the Wnt/β-catenin signaling pathway in the development of HCC.Frontiers in immunology · 2025Review
- From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- The FABD domain is critical for the oncogenicity of BCR/ABL in chronic myeloid leukaemia.Cell communication and signaling : CCS · 2024Article
- Mouse Models for Application in Colorectal Cancer: Understanding the Pathogenesis and Relevance to the Human Condition.Biomedicines · 2022Review
- Colorectal cancer: the APC-lncRNA link.The Journal of clinical investigation · 2019Article
- Functions of the APC tumor suppressor protein dependent and independent of canonical WNT signaling: implications for therapeutic targeting.Cancer metastasis reviews · 2018Review
- Interaction between APC and Fen1 during breast carcinogenesis.DNA repair · 2016Review
- Molecular mechanism of adenomatous polyposis coli-induced blockade of base excision repair pathway in colorectal carcinogenesis.Life sciences · 2015Review
- β-Catenin Signaling and Roles in Liver Homeostasis, Injury, and Tumorigenesis.Gastroenterology · 2015Review
- A pilot study evaluating genetic alterations that drive tobacco- and betel quid-associated oral cancer in Northeast India.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Nuclear adenomatous polyposis coli suppresses colitis-associated tumorigenesis in mice.Carcinogenesis · 2014Article
- Article
- MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer.Cancer cell · 2014Article
- A knock-in mouse model reveals roles for nuclear Apc in cell proliferation, Wnt signal inhibition and tumor suppression.Oncogene · 2012Article
- The transcription factor c-Jun protects against liver damage following activated β-Catenin signaling.PloS one · 2012Article
- Dickkopfs and Wnt/β-catenin signalling in liver cancer.World journal of clinical oncology · 2011Article
- Role of Wnt/β-catenin signaling in liver metabolism and cancer.The international journal of biochemistry & cell biology · 2011Review
- Mechanisms Regulating Microtubule Binding, DNA Replication, and Apoptosis are Controlled by the Intestinal Tumor Suppressor APC.Current colorectal cancer reports · 2011Article
- Assembly of the base excision repair complex on abasic DNA and role of adenomatous polyposis coli on its functional activity.Biochemistry · 2011Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsThe APC tumor suppressor is well known for its ability to regulate Wnt signaling through mediation of beta-catenin levels in the cell. Transient over expression of the tumor suppressor gene APC in colon cancer cells prevents entry into S phase of the cell cycle, a phenotype only partially restored by cotransfection of a transcriptionally active form of beta-catenin. In an attempt to define its transcription-independent tumor suppressor functions, we tested whether APC directly affects DNA replication.
methodsA transcriptionally quiescent in vitro DNA replication system, the polymerase chain reaction, DNA binding assays, and transient transfections in colon cancer cell lines were used to determine the effects of APC on DNA replication and the mechanism by which it works.
resultsWe report that exogenous full-length APC inhibits replication of template DNA through a function that maps to amino acids 2140-2421, a region of the protein commonly lost by somatic or germline mutation. This segment of APC directly interacts with DNA, while mutation of the DNA-binding S(T)PXX motifs within it abolishes DNA binding and reduces inhibition of DNA replication. Phosphorylation of this segment by cyclin-dependent kinases also reduces inhibition of DNA replication. Furthermore, transient transfection of an APC segment encoding amino acids 2140-2421 into a colon cancer cell line with mutant APC prevents cell cycle progression into or through S phase.
conclusionsOur results suggest that APC can negatively regulate cell cycle progression through inhibition of DNA replication by direct interaction with DNA.
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Registered trials
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