Glucose and Inositol Transporters, SLC5A1 and SLC5A3, in Glioblastoma Cell Migration
CANCERS(2022)
摘要
Simple Summary Cell migration is the main obstacle to the treatment of highly invasive brain cancer glioblastoma multiforme (GBM). We investigated in vitro the potential role of two solute carrier proteins (SLCs), SLC5A1 and SLC5A3, and their respective substrates, glucose and inositol, in GBM cell migration. We found that GBM cell motility was increased by medium supplementation with glucose and inositol and was strongly impaired by inhibition of SLC5A1/3 proteins. Using conventional and super-resolution fluorescence microscopy, we showed that both SLCs were not only highly expressed in migrating GBM cells, but they also localized to the lamellipodia, i.e., the migration-governing cell protrusions. Taken together, our data suggest that SLC5A1 and SLC5A3 are involved in GBM cell migration, presumably by mediating solute transport, osmotic water fluxes and thus local volume regulation in the lamellipodium. (1) 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) 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) 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.
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关键词
volume regulation,transportome,phlorizin
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