Cytoskeletal network in colon cancer: from genes to clinical application.
Colorectal cancer arises from well-defined sequential steps characterised by distinct genetic events. Abnormalities in the expression and functional activity of cell adhesion molecules are implicated in the development and progression of the majority of colorectal cancers. Intercellular (e.g. E-cadherin/catenin complex) and cell-matrix (e.g. integrins) adhesion molecules are more than just cementing substances but regulate cell polarity, differentiation, proliferation, migration and invasion. Many of these cellular events are mediated through their intimate association with the actin cytoskeletal network. A dynamic actin cytoskeleton characterises normal epithelial cells and polymerisation and depolymerisation of actin filaments enables cell shape to change during migration and mitosis. In colorectal cancer, cells lose actin cytoskeletal organisation and normal cell adhesion when they become invasive. Future investigations should allow the unravelling of new cytoskeletal network functions in tumour biology and may lead to the development of novel therapeutic strategies based on the manipulation of its associated molecules.
Buda
Andrea
A
Department of Pathology and Microbiology, Division of Histopathology, University of Bristol, Bristol Royal Infirmary, UK.
Pignatelli
Massimo
M
D000199:Actins / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism / Q000648:ultrastructure; D015820:Cadherins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D051177:Catenins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000209:etiology* / Q000235:genetics / Q000628:therapy; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology*; D051180:Desmoplakins; D005260:Female; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D051178:alpha Catenin; D051176:beta Catenin; D000095002:Delta Catenin
D000199:Actins; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D002352:Carrier Proteins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D016023:Integrins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; C020324:fascin; D000095002:Delta Catenin