Glucose and Inositol Transporters, SLC5A1 and SLC5A3, in Glioblastoma Cell Migration

葡萄糖和肌醇转运蛋白 SLC5A1 和 SLC5A3 在胶质母细胞瘤细胞迁移中的作用

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作者:Philippa K Brosch, Tessa Korsa, Danush Taban, Patrick Eiring, Philipp Kreisz, Sascha Hildebrand, Julia Neubauer, Heiko Zimmermann, Markus Sauer, Ryo Shirakashi, Cholpon S Djuzenova, Dmitri Sisario, Vladimir L Sukhorukov

Background

The recurrence of glioblastoma multiforme (GBM) is mainly due to invasion of the surrounding brain tissue, where organic solutes, including glucose and inositol, are abundant. Invasive cell migration has been linked to the aberrant expression of transmembrane solute-linked carriers (SLC). Here, we explore the role of glucose (SLC5A1) and inositol transporters (SLC5A3) in GBM cell migration. (2)

Conclusion

We provide several lines of evidence for the involvement of SLC5A1 and SLC5A3 in GBM cell migration, thereby complementing the migration-associated transportome. Our findings suggest that SLC inhibition is a promising approach to GBM treatment.

Methods

Using immunofluorescence microscopy, we visualized the subcellular localization of SLC5A1 and SLC5A3 in two highly motile human GBM cell lines. We also employed wound-healing assays to examine the effect of SLC inhibition on GBM cell migration and examined the chemotactic potential of inositol. (3)

Results

While GBM cell migration was significantly increased by extracellular inositol and glucose, it was strongly impaired by SLC transporter inhibition. In the GBM cell monolayers, both SLCs were exclusively detected in the migrating cells at the monolayer edge. In single GBM cells, both transporters were primarily localized at the leading edge of the lamellipodium. Interestingly, in GBM cells migrating via blebbing, SLC5A1 and SLC5A3 were predominantly detected in nascent and mature blebs, respectively. (4)

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