Expression of cell cycle regulatory proteins in anoikis-resistant endothelial cells subjected to syndecan-4 gene silencing

• Grant number: 21/03072-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2022
• End date: July 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Carla Cristina Lopes de Azevedo
• Grantee: Bianca Zaia Franco Ferreira
• 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 cell adhesion to the extracellular matrix (ECM). Many tumor cells are resistant to anoikis, facilitating their invasion and contributing to tumor metastasis. Previous data from our laboratory showed that endothelial cells resistant to anokis show morphological changes, high proliferation rate, low adhesion to fibronectin, laminin and collagen IV, dysregulation of the cell cycle, accompanied by increased expression of syndecan-4 (SDC4). SDC4 is a central mediator in cell adhesion, migration and proliferation and can interact directly and indirectly with other ECM molecules and with cytoskeletal proteins during cancer progression and metastasis development. The remodeling of the cytoskeleton architecture during the cell cycle is crucial for precise division. Despite the importance of SDC4 in several cellular events, its specific role in the dysregulation of the cell cycle in tumor cells is still not completely elucidated. This present study seeks to understand the role of SDC4 in the progression of the cell cycle in endothelial cells resistant to anoikis that were subjected to the syndecan-4 gene silencing assay. Thus, wild endothelial cells (EC), parental endothelial cells resistant to anoikis (Adh-EC), endothelial cells resistant to anoikis silenced for the syndecan-4 gene (Adh shRNA-Syn4-EC) and endothelial cells transfected with the EJ oncogene - ras (EJ-ras EC) will be studied in relation to the expression of regulatory proteins expressed in the different phases of the cycle, such as Cdks, cyclins, some inhibitors (P21 and P27) and proteins of the cytoskeleton. Thus, this study will bring new subsidies for the understanding of the mechanisms of dysregulation of the cell cycle during the progression of cancer, which may assist in the development of new anticancer drugs and a better direction in the treatment of the disease. (AU)