Solute carrier family 2 member 3: A central mediator in aerobic glycolysis contributing to tumor malignant progression.

Abstract

The solute carrier family 2 member 3 (SLC2A3) gene, located on human chromosome 12p3.3, encodes the glucose transporter 3 protein, which exhibits a notably high affinity for glucose and a substantial capacity to ferry glucose from extracellular fluid into the cytoplasm across the plasma membrane. SLC2A3 is frequently upregulated in various tumors, playing a pivotal role in aerobic glycolysis and thereby furnishing vital energy for tumor sustenance and malignant advancement, particularly in adverse conditions. Importantly, SLC2A3 exerts influence on multiple signaling pathways, particularly through the establishment of several positive feedback loops that amplify oncogenic effects, solidifying its status as a key oncogene in numerous malignancies. Such upregulation contributes significantly to uncontrolled proliferation, migration, invasion, distant metastasis, poor prognosis, and chemoresistance. Encouraging research has pinpointed certain potent and synergistic treatment effects via novel small molecules, including microRNAs directly targeting SLC2A3 or impacting associated signaling pathways in some tumors, particularly in tumors exhibiting chemoresistance. Therefore, disrupting the SLC2A3-mediated aerobic glycolysis appears to be a practical and feasible strategy to augment chemotherapeutic efficacy and potentially reverse chemoresistance.