Multiple Roles of APC and its Therapeutic Implications in Colorectal Cancer

J Natl Cancer Inst. 2017 Aug 1;109(8):djw332. doi: 10.1093/jnci/djw332.

Abstract

Adenomatous polyposis coli (APC) is widely accepted as a tumor suppressor gene highly mutated in colorectal cancers (CRC). Mutation and inactivation of this gene is a key and early event almost uniquely observed in colorectal tumorigenesis. Alterations in the APC gene generate truncated gene products, leading to activation of the Wnt signaling pathway and deregulation of multiple other cellular processes. It has been a mystery why most patients with CRC retain a truncated APC protein, but accumulating evidence suggest that these C terminally truncated APC proteins may have gain of function properties beyond the well-established loss of tumor suppressive function. Here, we will review the evidence for both the loss of function and the gain of function of APC truncations and how together they contribute to CRC initiation and progression.

Publication types

  • Review

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics*
  • Cell Transformation, Neoplastic / genetics*
  • Colorectal Neoplasms / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Models, Genetic
  • Mutation*
  • Tumor Suppressor Proteins / genetics
  • Wnt Signaling Pathway / genetics
  • beta Catenin / genetics

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein
  • Tumor Suppressor Proteins
  • beta Catenin