[Molecular mechanism of cancer seeding: adhesion molecules and signal transduction networks].
Cancer is a chronic and progressive disease characterised by disturbances of growth, cellular differentiation and maintenance of tissue integrity. The latter phenomenon leads to invasion. The transition from the noninvasive towards the invasive stage of the disease is crucial because it transforms a benign and easily curable lesion into a malignant and therapy-resistant disease. Tumour progression is the result of a number of genetic alterations, initiated by a single mutation without immediate clinical manifestations and ending with a metastatic cascade. Activation of tumour-promoter genes (oncogenes), by mutation or overexpression, and inactivation of tumour-suppressor genes, by mutation or deletion, favour oncogenesis. Separate genes are implicated in distinct steps of the tumour progression. Defects in DNA-repair genes influence all steps. Metastasis is a multistep process of invasion. At each step invasion occurs within a micro-ecosystem in which a continuous molecular crosstalk takes place between the cancer cells and the host cells that participate at the establishment of the tumour. The cancer cells carry the genetic alterations and act as the founders of the micro-ecosystem. We shall discuss the invasion-suppressor function of the E-cadherin/catenin complex. Inactivation of one element of this complex may initiate invasion in an appropriate genetic background. Such inactivation may take place at various levels: mutation in coding sequences; hypermethylation of the promoter; mRNA instability; tyrosine phosphorylation; proteolysis; extracellular interactions.
Mareel
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Afdeling voor Experimentele Cancerologie, Vakgroep Radiotherapie en Kerngeneeskunde, Universitair Ziekenhuis Gent.
Vermeulen
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Bracke
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D015820:Cadherins / Q000235:genetics; D002273:Carcinogens; D015815:Cell Adhesion Molecules / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D018450:Disease Progression; D016147:Genes, Tumor Suppressor; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009366:Neoplasm Seeding; D009369:Neoplasms / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics; D017354:Point Mutation; D015398:Signal Transduction
D015820:Cadherins; D002273:Carcinogens; D015815:Cell Adhesion Molecules
Moleculaire mechanismen van kankeruitzaaiing: adhesie moleculen en netwerken van signaaltransductie.