IGFBP7 Fuels the Glycolytic Metabolism in B-Cell Precursor Acute Lymphoblastic Leukemia by Sustaining Activation of the IGF1R-Akt-GLUT1 Axis

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Jun 10

PMID 37298628

Authors

Leonardo Luis Artico

Juliana Silveira Ruas

Jose Ricardo Teixeira Junior

Natacha Azussa Migita

Gustavo Seguchi

Xinghua Shi

Silvia Regina Brandalise

Roger Frigerio Castilho

Jose Andres Yunes

Affiliations

Soon will be listed here.

Abstract

Increased glycolytic metabolism plays an important role in B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL). We previously showed that IGFBP7 exerts mitogenic and prosuvival effects in ALL by promoting IGF1 receptor (IGF1R) permanence on the cell surface, thus prolonging Akt activation upon IGFs/insulin stimulation. Here, we show that sustained activation of the IGF1R-PI3K-Akt axis concurs with GLUT1 upregulation, which enhances energy metabolism and increases glycolytic metabolism in BCP-ALL. IGFBP7 neutralization with a monoclonal antibody or the pharmacological inhibition of the PI3K-Akt pathway was shown to abrogate this effect, restoring the physiological levels of GLUT1 on the cell surface. The metabolic effect described here may offer an additional mechanistic explanation for the strong negative impact seen in ALL cells in vitro and in vivo after the knockdown or antibody neutralization of IGFBP7, while reinforcing the notion that it is a valid target for future therapeutic interventions.

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