Functional Investigation of IGF1/IRS1 signaling pathway in acute lymphoblastic leukemia

• Grant number: 14/14844-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): January 01, 2017
• Effective date (End): August 08, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Fabíola Traina
• Grantee: Ana Paula Nunes Rodrigues Alves
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Acute lymphoblastic leukemia (ALL) is a neoplasm of immature lymphoid cells, characterized by failure of differentiation, increased cell proliferation and resistance to apoptosis. The treatment of ALL in adults is currently performed with multiple chemotherapeutics, but the overall survival is still poor. The study of cell signaling pathways involved in the pathophysiology of the disease allows the future development of new therapies. The IGF1R/IRS1 signaling pathway is related to the development and progression of solid tumors. This signaling pathway is initiated by the binding of the ligand (IGF1) to its receptor (IGF1R) with subsequent activation of its substrates, which includes the insulin receptor substrate 1 (IRS1). Recent evidences indicate that the IGF1R/IRS1 signaling pathway activates PI3K/AKT/mTOR and MAPK, participates in hematological malignancies, and may act as oncogenes inducing malignant transformation in acute myeloid leukemia and chronic lymphocytic leukemia. Thus, our goal is to investigate the role of IGF1R and IRS1 in ALL. Acute lymphoblastic leukemia cell lines or primary cells will be submitted to IGF1R or IRS1 inhibition through inhibitory drugs. Western blotting analysis and functional studies will be used to assess the impact of IGF1R or IRS1 inhibition on PI3K/AKT/mTOR and MAPK signaling pathways, and on leukemic cell phenotype. We hypothesize that the signaling pathway IGF1R/IRS1 participates in the ALL phenotype through activation of PI3K/AKT/mTOR and MAPK signaling pathways.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NUNES RODRIGUES ALVES, ANA PAULA; FERNANDES, JAQUELINE CRISTINA; FENERICH, BRUNA ALVES; COELHO-SILVA, JUAN LUIZ; SCHEUCHER, PRISCILA SANTOS; SIMOES, BELINDA PINTO; REGO, EDUARDO MAGALHAES; RIDLEY, ANNE J.; MACHADO-NETO, JOAO AGOSTINHO; TRAINA, FABIOLA. IGF1R/IRS1 targeting has cytotoxic activity and inhibits PI3K/AKT/mTOR and MAPK signaling in acute lymphoblastic leukemia cells. Cancer Letters, v. 456, p. 59-68, 2019. (14/14844-9, 14/50947-7, 13/08135-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ALVES, Ana Paula Nunes Rodrigues. Functional investigation of IGF1/IRS1 signaling pathway in acute lymphoblastic leukemia. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.