Wnt signalling and the actin cytoskeleton.
The tumour suppressor adenomatous polyposis coli (APC) is mutated in sporadic and familial colorectal tumours. APC binds to beta-catenin, a key component of the Wnt signalling pathway, and induces its degradation. In addition to this role, there is increasing evidence for additional roles of APC, including the organization of cytoskeletal networks. APC interacts with microtubules and accumulates at their plus ends in membrane protrusions. Also, it has been reported that APC is associated with the plasma membrane in an actin-dependent manner. Moreover, APC interacts with IQGAP1, an effector of Rac1 and Cdc42, and APC-stimulated guanine nucleotide exchange factor (Asef), a Rac1-specific guanine nucleotide exchange factor (GEF). IQGAP1 mediates association of APC with cortical actin in the leading edge of migrating cell and both proteins are required for cell polarization and directional migration. APC interacts with Asef and stimulates its activity, thereby regulating the actin cytoskeletal network, cell morphology, adhesion and migration. Truncated mutant APCs present in colorectal tumour cells activate Asef constitutively and contribute to their aberrant migratory properties, which may be important for adenoma formation as well as tumour progression to invasive malignancy.
Akiyama
T
T
Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. akiyama@imcbns.iam.u-tokyo.ac.jp
Kawasaki
Y
Y
D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D017491:Genes, APC; D016147:Genes, Tumor Suppressor; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*
D000199:Actins; C509805:KIF2A protein, human; D051153:Wnt Proteins; D016547:Kinesins