| Full text | |
| Author(s): |
Artico, Leonardo Luis
;
Ruas, Juliana Silveira
;
Teixeira Junior, Jose Ricardo
;
Migita, Natacha Azussa
;
Seguchi, Gustavo
;
Shi, Xinghua
;
Brandalise, Silvia Regina
;
Castilho, Roger Frigerio
;
Yunes, Jose Andres
Total Authors: 9
|
| Document type: | Journal article |
| Source: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 24, n. 11, p. 14-pg., 2023-06-02. |
| 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. (AU) | |
| FAPESP's process: | 19/04943-3 - IGFBP7 action on TGFb/p53 pathways and corticoids resistance in Acute Lymphoblastic Leukemia |
| Grantee: | Leonardo Luís Artico |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 22/04464-0 - Insulin signaling in metabolic diseases: the role of IGFBP7 in adipose tissue metabolic function |
| Grantee: | Leonardo Luís Artico |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |
| FAPESP's process: | 17/17728-8 - Mitochondrial function and dysfunction: implications for aging and associated diseases |
| Grantee: | Aníbal Eugênio Vercesi |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 14/20015-5 - Aberrant IL7R signaling in leukemogenesis: from the basics to potential therapeutics |
| Grantee: | José Andrés Yunes |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 12/12802-1 - Cooperating mutations, functional studies and antibodies against the mutant IL7R in acute lymphoblastic leukemia |
| Grantee: | José Andrés Yunes |
| Support Opportunities: | Regular Research Grants |