Structure and major functions of both the full-length and truncated adenomatous polyposis coli (APC) gene

(A) Full-length APC proteins contain multiple domains, including oligomerization domain, an armadillo repeat-domain, a 15- or 20-residue repeat domain important for binding to beta-catenin, SAMP repeats for axin binding, a basic domain for microtubule binding, and C-terminal domains that bind to EB1 protein. Due to its numerous interactions with a variety of proteins, APC is involved in cellular processes related to cell migration,
adhesion, proliferation, differentiation, and chromosomal segregation. Most APC mutations occur within MCR.
(B) The C-terminally truncated proteins present in colorectal cancer lack the domains that are required for binding to microtubules, EB1, and beta-catenin, thus leading to the induction of chromosomal instability, activation of proliferation, and inhibition of differentiation. Truncated APC may have dominant properties that lead to stronger stimulation of cell migration and promotion of cellular survival.