INVESTIGATION OF THE FUNCTIONS OF RHOA AND RHOC GTPASES IN THE ADHESION AND MIGRATION OF LEUKEMIA CELLS

• Grant number: 24/09541-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: January 05, 2025
• End date: January 04, 2026
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Mariana Lazarini
• Grantee: Stephany Suelen de Castro Sampaio
• Supervisor: Sandrine Etienne-Manneville
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: Institut Pasteur, France
• Associated to the scholarship: 22/07033-0 - Study of Rho function in DNA damage repair and migration of Acute Myeloid Leukemia cells and its association with p53 signaling pathway, BP.DD

Abstract

Proliferation and survival of immature hematopoietic stem cells rely on their bi-directional interactions with components of the bone marrow microenvironment. These interactions also occur in leukemia stem cells and are essential for leukemia development and therapy response. The Rho GTPase family of proteins plays a crucial role in regulating cellular adhesion and migration, through the regulation of cytoskeletal dynamics. However, the role of Rho GTPases has been poorly explored in leukemia. We hypothesize that RhoA or RhoC signaling are recruited in the communication between leukemia cells and the bone marrow microenvironment to regulate cell adhesion and migration. Therefore, our aim in this study is to evaluate the effects of RhoA or RhoC silencing on the adhesion and migration process of leukemia cells on different niche components (proteins and stromal cells). Cell adhesion and migration will be evaluated in vitro using time lapse microscopy with myeloid cell lines (U937 and OCI-AML3) stably silenced for RhoA or RhoC with lentivirus. HS-5 cell line will be used as a model of stromal cells. The elucidation of the specific contributions of RhoA and RhoC GTPases to leukemia cell adhesion and migration will contribute to understand the mechanism used by leukemia cells for survival and proliferation in the bone marrow microenvironment. The envisaged outcomes hold the potential to catalyze the development of innovative therapeutic avenues for leukemia targeting Rho GTPasesto enhance patient outcomes and well-being.