Expression of anti and pro-apoptotic genes and proteins in anoikis-resistant rabbit aortic endothelial cells after silencing of the PIK3CA gene (phosphatidylinositol-3-kinase, alpha catalytic subunit)

• Grant number: 18/04468-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2018
• End date: December 31, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Carla Cristina Lopes de Azevedo
• Grantee: Amanda da Silva Cruz
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

Anoikis is a type of regulated cell death that occurs due to lack of adhesion or inadequate adhesion of the cell to the extracellular matrix (ECM). Many tumor cells are resistant to anoikis and this facilitates the invasion of these cells contributing to tumor metastasis. Although it is an important process, the mechanisms involved in regulating resistance to anoikis have not yet been fully elucidated. Previous data from our laboratory have shown that endothelial cells resistant to anoikis present morphological changes, high proliferation rate, low adhesion to fibronectin, laminin and collagen IV, and cell cycle dysregulation. In addition, anoikis-resistant cell lines exhibit a high invasive potential, low apoptosis rate, increased expression of Sindecam-4 and Heparanase, as well as increased expression of PI3K, Akt, ERK and H-ras. Altered PI3K signaling may contribute to the development of cancer. The objective of this study is to evaluate the role of the PIK3CA gene that encodes the PI3K p110 alpha subunit in the genetic and protein expression of molecules involved in the regulation of apoptosis in anoikis resistant endothelial cells, since the understanding of the apoptotic mechanisms in these cells will allow the development of new strategies in the treatment of cancer.