Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
Sci Rep. 2024 Oct 3;14(1):23031. doi: 10.1038/s41598-024-74249-z.
Tumor cells promote malignant behaviors such as proliferation, invasion, and metastasis of cancer cells through glucose metabolic reprogramming, but the role of the H-dependent sugar cotransporter SLC45A4 in regulating metabolic reprogramming in ovarian cancer (OC) remains largely unknown. This study aimed to investigate the effects of SLC45A4 silencing on the transcriptome spectrum of ovarian cancer cells (OCC), glucose uptake, lactic acid production, intracellular ATP levels, and the expression and activity of HIF-α glycolysis signaling pathway. The results showed that SLC45A4 is overexpressed in OC and its elevated expression correlates with adverse clinical outcomes in OC patients. Silencing of SLC45A4 significantly inhibited the proliferation, invasion, and metastasis of OCC by suppressing glucose uptake and glycolysis, and it also reduced the expression of HIF-α glycolysis signaling pathway in OC tissues. In vivo experiments using shRNA to knock down SLC45A4 in xenograft models in nude mice demonstrated a significant inhibition of tumor growth. These findings suggest that SLC45A4 silencing can restrain the malignant progression of OC by inhibiting glucose uptake in OCC and affecting the reprogramming of glycolytic energy metabolism, indicating that SLC45A4 may serve as a potential therapeutic target for OC intervention.
肿瘤细胞通过葡萄糖代谢重编程促进癌细胞的增殖、侵袭和转移等恶性行为，但 H+依赖型糖共转运蛋白 SLC45A4 在调节卵巢癌（OC）代谢重编程中的作用在很大程度上尚不清楚。本研究旨在探讨 SLC45A4 沉默对卵巢癌细胞（OCC）转录组谱、葡萄糖摄取、乳酸生成、细胞内 ATP 水平以及 HIF-α糖酵解信号通路表达和活性的影响。结果表明，SLC45A4 在 OC 中过度表达，其表达水平升高与 OC 患者的不良临床结局相关。沉默 SLC45A4 可通过抑制葡萄糖摄取和糖酵解显著抑制 OCC 的增殖、侵袭和转移，还可降低 OC 组织中 HIF-α糖酵解信号通路的表达。在裸鼠异种移植模型中使用 shRNA 敲低 SLC45A4 的体内实验表明，肿瘤生长受到显著抑制。这些发现表明，SLC45A4 沉默通过抑制 OCC 中的葡萄糖摄取和影响糖酵解能量代谢的重编程，可以抑制 OC 的恶性进展，提示 SLC45A4 可能成为 OC 干预的潜在治疗靶点。
