CIN By WNT: growth pathways, mitotic control and chromosomal instability in cancer.
There is mounting evidence suggesting that an instable genome is directly involved in the development of cancer. The predominant form of genomic instability in most cancers presents itself as an increased rate of loss or gain in chromosome number and parts, referred to as chromosomal instability (CIN). Indeed, mutations in components of mitotic checkpoints have been described in human cancers, albeit in low numbers, suggesting that although CIN principally arises due to defective surveillance of mitosis, its molecular causes remain largely unclear. We have recently shown that the Wnt/beta-catenin signaling pathway, whose aberrant activation has been established as the driving force of tumorigenesis in many cancers particularly colorectal cancer, can generate CIN through the transcriptional target gene conductin/axin2. Here we propose a model for the generation of CIN by aberrant Wnt/beta-catenin signaling and we suggest that growth pathways not only control cell cycle progression through G(1)/S transition but have also evolved cross talks to regulate mitosis. We speculate that aberrant activation of these pathways, as observed in cancer can result in chromosomal instability thus explaining the widespread appearance of CIN in human cancers.
Hadjihannas
Michel V
MV
Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nürnberg, Erlangen, Germany.
Behrens
Jürgen
J
D000818:Animals; D060466:Axin Protein; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D043171:Chromosomal Instability / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D018816:Genes, cdc / Q000502:physiology; D006801:Humans; D008938:Mitosis / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics*; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
C491761:AXIN2 protein, human; D060466:Axin Protein; D003598:Cytoskeletal Proteins; D051153:Wnt Proteins; D051176:beta Catenin