Microenvironmental regulation of E-cadherin-mediated adherens junctions.
The interaction between tumor cells and the microenvironment has substantial effects on tumor cell behavior by influencing cell-cell as well as cell-matrix contacts. The underlying molecular mechanisms are only partially unraveled. In this review we focus on the influence of the stromal microenvironment, especially collagen type I and type III on cellular adhesion and epithelial to mesenchymal transition (EMT). Extensive studies have emphasized that components of the microenvironment such as fibrillar collagen or growth factors like transforming growth factor beta are involved in induction of dedifferentiation of epithelial cells accompanied by disruption of the E-cadherin adhesion complex and reduced E-cadherin concentrations. On the molecular level many different proteins have been identified which are involved in the regulation of EMT, such as activation of integrins, intracellular kinases such as Src, focal adhesion kinase (FAK) or phosphatidylinositol-3 kinase (PI3-kinase) and alteration of catenin phosphorylation. The reduced cellular adhesion influences the tissue integrity and allows tumor cells to disseminate from the primary tumor representing an early step in cancer metastasis.
Giehl
Klaudia
K
Department of Internal Medicine I, University of Ulm, D-89081 Ulm, Germany.
Menke
Andre
A
D000199:Actins / Q000502:physiology; D022005:Adherens Junctions / Q000502:physiology*; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D018450:Disease Progression; D004847:Epithelial Cells / Q000502:physiology; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D016023:Integrins / Q000502:physiology; D008648:Mesoderm / Q000502:physiology; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction; D020703:ras GTPase-Activating Proteins / Q000502:physiology
D000199:Actins; D015820:Cadherins; C101203:IQ motif containing GTPase activating protein 1; D016023:Integrins; D020703:ras GTPase-Activating Proteins