CCL2 activates AKT signaling to promote glycolysis and chemoresistance in glioma cells.

Abstract

The incidence of gliomas is increasing. Although great progress in glioma treatment has been made, the clinical outcome remains unsatisfactory. Chemokine (C-C motif) ligand 2 (CCL2) plays a key role in different types of cancers, including glioma. However, the function of CCL2 in glioma chemoresistance is not fully understood. In the current study, CCL2 was significantly upregulated in glioma. More importantly, CCL2 and CCR2 were significantly upregulated in temozolomide (TMZ)-resistant glioma. TMZ-resistant malignant glioblastoma cells (U251/TMZ) had higher expressions of CCL2 and CCR2 and a higher level of glycolysis as compared to its parental cell line U251. Silencing of CCL2 in U251/TMZ cells inhibited glycolysis. Overexpression of CCL2 reduced TMZ-induced apoptosis through activation of the AKT pathway and promotion of glycolysis. Moreover, overexpression of CCL2 significantly reduced the antitumor effect of TMZ in vivo. In conclusion, CCL2 overexpression reduced the antitumor effect of TMZ by enhancing glycolysis through activation of AKT signaling. The findings highlighted the importance of CCL2/CCR2/glycolysis and its potential value in developing new treatment for glioma.

• Authors: Yafang Qian, Peng Ding, Jie Xu, Xiaohu Nie, Bin Lu
• Journal: Cell biology international (Cell Biol Int) Vol. 46 Issue 5 Pg. 819-828 (May 2022) ISSN: 1095-8355 [Electronic] England
• PMID: 35178826 (Publication Type: Journal Article)
• Copyright: © 2022 International Federation for Cell Biology.

Chemical References

• CCL2 protein, human
• Chemokine CCL2
• Proto-Oncogene Proteins c-akt
• Temozolomide

Topics

• Apoptosis
• Brain Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Chemokine CCL2 (metabolism)
• Drug Resistance, Neoplasm
• Glioma (metabolism)
• Glycolysis
• Humans
• Proto-Oncogene Proteins c-akt (metabolism)
• Temozolomide (pharmacology, therapeutic use)