The Role of APC in Mitosis and in Chromosome Instability

Interactions and functions of the adenomatous polyposis coli (APC) protein at a glance

“…Changes in cytoskeletal regulation that result from loss of APC lead to decreased migration, which reduces the elimination of cells from the challenging environment of the intestinal tract (Nelson et al, 2012). In addition, changes in cytoskeletal regulation also underpin defects in mitotic spindles and mitotic checkpoints that can promote genetic instability, an important contributor to tumorigenesis (Caldwell and Kaplan, 2008;Caldwell and Kaplan, 2009;Dikovskaya et al, 2007).…”

“…The ability of APC to bind to itself also contributes to its effect on cell migration (Li et al, 2008). Changes in cytoskeletal interaction of APC underpin defects in mitotic spindles and mitotic checkpoints to promote genetic instability, a major contributing factor to tumorigenesis (Caldwell and Kaplan, 2008;Caldwell and Kaplan, 2009;Dikovskaya et al, 2007). Moreover, changes in microtubules in cells with mutant APC contribute to changes in how cells extrude during the process of their elimination from epithelia.…”

APC as a mobile scaffold: Regulation and function at the nucleus, centrosomes, and mitochondria

“…APC regulates colon cancer initiation and progression in several ways, and the best characterized of these include its control of Wnt signaling (via control of b-catenin turnover), mitosis (via control of spindle orientation and chromosome segregation), and cell migration (2)(3)(4)(5)(6)(7)(8). These roles are all impacted by APC mutations (3,6).…”

Adenomatous Polyposis Coli (APC) Regulates Multiple Signaling Pathways by Enhancing Glycogen Synthase Kinase-3 (GSK-3) Activity

“…For example, APC and GSK-3 are both required for proper spindle formation during mitosis (32,34,35). As APC promotes phosphorylation of ␤-catenin, a direct GSK-3 substrate, and is involved in many of the same processes as GSK-3, we hypothesized that APC regulates additional GSK-3 substrates and GSK-3-dependent signaling pathways.…”