This study evaluated the expression pattern of GLUT10 (gene SLC2A10) using public transcriptomic resources. Pan-cancer analysis with GEPIA2 combining TCGA and GTEx data identified tissues in which GLUT10 expression differed from normal: it was decreased in adrenocortical carcinoma, cervical squamous cell carcinoma and adenocarcinoma, and kidney chromophobe tumor tissues, and increased in invasive breast cancer, glioma, skin melanoma, and thymoma. Focused analysis with the UALCAN platform showed that SLC2A10 mRNA levels in breast cancer tissues were 1.85-fold higher than in normal breast tissues (P < 0.001), indicating upregulation of GLUT10 in breast tumors at the mRNA level.
The authors measured SLC2A10 mRNA across a panel of breast cancer cell lines using RT-qPCR. Reported mean expression values (±SD) ranked from highest to lowest were: Hs578T (160.5 ± 12.3), SK-BR-3 (115.2 ± 10.5), MDA-MB-468 (50.1 ± 5.2), T-47D (35.4 ± 4.1), and MCF7 (25.6 ± 3.8). All cancer cell lines showed significantly higher SLC2A10 mRNA compared with normal breast epithelial cells (P < 0.001), supporting cell-line evidence for elevated SLC2A10 expression in breast cancer models.
In vitro functional experiments used two breast cancer cell lines with complementary manipulations of SLC2A10. SK-BR-3 cells were transfected with either non-targeting scrambled shRNA (shScr) or two independent shRNAs targeting SLC2A10 (shSLC2A10#1 and shSLC2A10#2). MDA-MB-231 cells were transfected with an empty vector control or a full-length SLC2A10 overexpression construct.
Molecular and cellular assays included RT-qPCR to quantify SLC2A10 mRNA, western blotting to assess GLUT10 protein and cleaved caspase-3, and the CM-H2DCFDA fluorescent probe to measure intracellular reactive oxygen species (ROS) levels. Functional endpoints relevant to chemotherapy response were drug sensitivity assays and colony formation assays to evaluate cisplatin sensitivity, and flow cytometry to quantify apoptosis.
Compared with the shScr control, both shSLC2A10#1 and shSLC2A10#2 produced measurable biological effects in SK-BR-3 cells. Knockdown increased intracellular ROS levels, reported as relative fluorescence intensity values of 1.78 ± 0.12 and 2.05 ± 0.15 for shSLC2A10#1 and shSLC2A10#2, respectively (P < 0.05). SLC2A10 knockdown also increased sensitivity to cisplatin, reduced the number of colonies in colony formation assays, and potentiated cisplatin-induced ROS accumulation and apoptosis. These findings indicate that reducing GLUT10 expression sensitizes SK-BR-3 cells to cisplatin and promotes chemotherapy-induced oxidative stress and cell death.
In the reciprocal experiment, overexpressing SLC2A10 in MDA-MB-231 cells produced opposite effects to knockdown. SLC2A10 overexpression decreased intracellular ROS (relative fluorescence intensity 0.58 ± 0.09, P < 0.05) compared with vector control. Overexpression reduced cisplatin sensitivity and inhibited cisplatin-induced ROS accumulation and apoptosis. These observations support a model in which higher GLUT10 levels mitigate ROS accumulation and blunt cisplatin cytotoxicity in these breast cancer cells.
Protein-level data were obtained by western blot for GLUT10 and cleaved caspase-3; the latter was used as a marker of apoptosis activation in response to cisplatin. ROS was quantified using the CM-H2DCFDA fluorescent probe and reported as relative fluorescence intensity. Drug sensitivity was assessed by drug sensitivity assays and clonogenic survival was evaluated by colony formation assays. Flow cytometry provided quantitative apoptosis rates. Across these measures, altering SLC2A10/GLUT10 expression produced consistent changes in ROS, apoptosis markers, and functional cisplatin response, with knockdown increasing ROS and apoptosis and overexpression decreasing them.
The authors conclude that GLUT10 is highly expressed in breast cancer and that it mediates cisplatin resistance at least in part by regulating intracellular ROS levels. Knockdown of SLC2A10 enhanced cisplatin sensitivity and promoted ROS accumulation and apoptosis, while overexpression had protective effects against cisplatin. Based on these results, the study suggests that SLC2A10/GLUT10 may be a potential molecular target for reversing cisplatin resistance in breast cancer and could inform strategies for individualized therapy.
All authors declared no conflicts of interest.
Note: This summary and rewrite reflect data, methods, and results as reported in the source PubMed abstract. Detailed experimental protocols, statistical analyses beyond the reported P values, and full data figures were not included in the abstract and therefore are not reported here.