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Journal of Cancer Research and Clinical Oncology

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01.11.2010 | Original Paper

PI3K/Akt and GSK-3β prevents in a differential fashion the malignant phenotype of colorectal cancer cells

verfasst von: Wallace Martins de Araújo, Flavia Castello Branco Vidal, Waldemir Fernandes de Souza, Julio César Madureira de Freitas Junior, Wanderley de Souza, Jose Andres Morgado-Diaz

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 11/2010

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Abstract

Purpose

During colorectal cancer progression, the loss of differentiation and cell–cell adhesion as well as a higher migratory potential are well-defined features; however, the signaling mechanism governing these events is not fully elucidated. The aim of this study was to investigate the role that PI3K and downstream effectors play in controlling colon cancer malignant phenotypes.

Methods

HCT-116 cells, a human model of colon cancer, which are highly metastatic and undifferentiated, were treated with LY294002, a specific inhibitor of PI3K. Cell differentiation and apical junctional complex (AJC) formation were monitored using alkaline phosphatase and electron microscopy analysis. Immunofluorescence and Western blotting were used to accompany the subcellular localization of AJC proteins. PI3K downstream molecules were analyzed by western blotting, and proliferation, wound healing, and colony formation techniques to determine malignant phenotype alterations.

Results

PI3K inhibition increased alkaline phosphatase activity, led to an enterocyte-like growth and formed a functional AJC. LY294002 treatment was able to recruit E-cadherin, β-catenin, claudin-3, and ZO-1 to the cell–cell contact region, and this effect was essential for AJC assembly and association of these proteins to the cytoskeleton. Furthermore, we provided evidence that PI3K inhibition leads to a decrease in p-Akt and p-GSK-3β and increased p-β-catenin levels, which in turn controlled cell proliferation, motility, and colony formation.

Conclusion

Our results demonstrate that PI3K/Akt and GSK-3β prevents in a differential fashion the malignant phenotype of HCT-116 colorectal cancer cells, which could constitute a potential therapeutic target for treatment of this cancer type.

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Titel: PI3K/Akt and GSK-3β prevents in a differential fashion the malignant phenotype of colorectal cancer cells
verfasst von: Wallace Martins de Araújo
Flavia Castello Branco Vidal
Waldemir Fernandes de Souza
Julio César Madureira de Freitas Junior
Wanderley de Souza
Jose Andres Morgado-Diaz
Publikationsdatum: 01.11.2010
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 11/2010
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-010-0836-5

Springer Medizin

PI3K/Akt and GSK-3β prevents in a differential fashion the malignant phenotype of colorectal cancer cells