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The Role of β‐catenin in cell division and colon cancer
Author(s) -
Alba Nancy,
Anderson Darrell,
Cargile TeAngelo,
Rodriguez Giovanni,
Romero Karla,
Johnson Carol,
Narayan Malathi,
Twining Sally
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb178
Subject(s) - wnt signaling pathway , cell division , cell , survivin , microbiology and biotechnology , cell growth , cancer research , catenin , asymmetric cell division , biology , chemistry , cancer , signal transduction , genetics
Colon cancer is the fourth most lethal cancer in the U.S. As food passes through the colon, water and vitamins are absorbed and epithelial cells are sloughed off and replaced by a tightly regulated cell division process. Unregulated cell division can lead to the formation of polyps and tumors. β‐catenin plays a role in regulating cell division and was modeled by the Messmer SMART Team (Students Modeling A Research Topic) using 3D printing technology. In non‐dividing cells, a multi‐protein complex of APC, GSK‐3 and Axin phosphorylates β‐catenin, signaling its degradation and preventing cell division. When cell division is needed, a Wnt signal cascade causes the complex to release β‐catenin, stabilizing the protein for nuclear translocation and binding to TCF, a transcriptional activator, thus triggering cell division. Competitive binding of the inhibitor proteins, ICAT and Chibby, to β‐catenin negatively regulates this process. In colon cancer, mutations in APC or Axin impede binding of the complex to β‐catenin, preventing degradation, leading to increased nuclear localization, binding to TCF and deregulated cell division. Additionally, survivin, an anti‐apoptotic protein that enables tumor cell survival, is upregulated. Understanding β‐catenin's structure could help design drugs to promote binding of inhibitors to prevent the unregulated cell division of cancer. Supported by a grant from NIH‐NCRR‐SEPA.