Functional assessment of syndecan-4 and PIK3CA (phosphatidylinositol 4,5-bisphosphate 3-kinase, catalytic subunit alpha) genes in anoikis-resistant endothelial cells.

Abstract

The resistance of tumor cells to cell death by adhesion loss (anoikis) is a major cellular feature that contributes to tumor progression and metastasis. As a functional phenomenon, anoikis resistance is an important event in the metastatic cascade, a prerequisite for colonization and spread to distant sites. However, the mechanisms involved in anoikis regulation resistance are not fully elucidated. Various molecules are involved in the survival processes, cell adhesion and proliferation, including the syndecan-4, a heparan sulfate proteoglycan (PGHS) and phosphatidylinositol 3-kinase (PI3K). Changes in syndecan-4 expression have been commonly found in tumor cells, indicating their involvement in cancer. Also, numerous studies reveal that many components of the PI3K pathway are the target of mutations in several types of human tumors. Previous data from our laboratory showed that anoikis-resistant endothelial cells exhibit overexpression of syndecan-4 and PI3K (p110 alpha). These and other findings suggest that syndecan-4 and PI3K are suitable for pharmacological intervention, as attractive targets for cancer therapy. Therefore, to analyze the role of these molecules in different events such as, proliferation, adhesion, cell invasion and apoptosis, we will perform the silencing of syndecan-4 and PIK3CA genes, individually, in anoikis-resistant endothelial cells. These results should help to understand the function of genes in adhesion and proliferation processes, cell cycle and apoptosis of endothelial cells. (AU)