Adenomatous polyposis coli (APC) plays multiple roles in the intestinal and colorectal epithelia

Takao Senda, Akiko Iizuka-Kogo, Takanori Onouchi, Atsushi Shimomura

Research output: Contribution to journalReview article

74 Citations (Scopus)

Abstract

The adenomatous polyposis coli (APC) gene is mutated in familial adenomatous polyposis and in most sporadic colorectal tumors. During both embryonic and postnatal periods, APC is widely expressed in a variety of tissues, including the brain and gastrointestinal tract. The APC gene product (APC) is a large multidomain protein consisting of 2843 amino acids. APC downregulates the Wnt signaling pathway through its binding to β-catenin and Axin. Most mutated APC proteins in colorectal tumors lack the β-catenin-binding regions and fail to inhibit Wnt signaling, leading to the overproliferation of tumor cells. Several mouse models (APC 580D , APC Δ716 , APC 1309 , APC Min , APC 1638T ) have been established to investigate carcinogenesis caused by APC mutations. APC also binds to APC-stimulated guanine nucleotide exchange factor, the kinesin superfamily-associated protein 3, IQGAP1, microtubules, EB1, and discs large (DLG). APC has both nuclear localization signals and nuclear export signals in its molecule, suggesting its occasional nuclear localization and export of β-catenin from the nucleus. APC is highly expressed in the intestinal and colorectal epithelia and may be involved in homeostasis of the enterocyte renewal phenomena, in which proliferation, migration, differentiation, and apoptosis are highly regulated both temporally and spatially. Through the many binding proteins mentioned, APC can exert multiple functions involved in epithelial homeostasis.

Original languageEnglish
Pages (from-to)68-81
Number of pages14
JournalMedical Molecular Morphology
Volume40
Issue number2
DOIs
Publication statusPublished - 01-06-2007

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Adenomatous Polyposis Coli
Intestinal Mucosa
Catenins
APC Genes
Colorectal Neoplasms
Adenomatous Polyposis Coli Protein
Homeostasis
Nuclear Export Signals
Guanine Nucleotide Exchange Factors
Kinesin
Nuclear Localization Signals
Wnt Signaling Pathway
Microtubule-Associated Proteins
Cell Nucleus Active Transport
Enterocytes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology

Cite this

Senda, Takao ; Iizuka-Kogo, Akiko ; Onouchi, Takanori ; Shimomura, Atsushi. / Adenomatous polyposis coli (APC) plays multiple roles in the intestinal and colorectal epithelia. In: Medical Molecular Morphology. 2007 ; Vol. 40, No. 2. pp. 68-81.
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Adenomatous polyposis coli (APC) plays multiple roles in the intestinal and colorectal epithelia. / Senda, Takao; Iizuka-Kogo, Akiko; Onouchi, Takanori; Shimomura, Atsushi.

In: Medical Molecular Morphology, Vol. 40, No. 2, 01.06.2007, p. 68-81.

Research output: Contribution to journalReview article

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