Shakartalla Sarra B, Bouzid Amal, Altaie Alaa M, Ashmawy Naglaa S, Al Shareef Zainab M, Husseiny Mohamed I, Soliman Sameh S M
Research Institute for Medical and Health Sciences, University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates.
College of Medicine, University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates.
Med Oncol. 2025 Jun 16;42(7):263. doi: 10.1007/s12032-025-02829-8.
Metastasis is the primary cause of death in women with breast cancer, which ranks among the most prevalent malignant diseases. Recently, we identified the significant metastatic role of hypoxanthine (HYP) in cancer cells. HYP is a naturally occurring purine derivative that actively participates in the synthesis of nucleic acids via the nucleotide salvage pathway. To gain a deeper insight onto the metastatic mechanism of HYP, integrated transcriptomics and metabolomics were conducted following the treatment of MCF-7 cells with HYP. HYP significantly activates PI3K/AKT pathway, a hallmark of cancer metastasis. Glycerolipid and fatty acid metabolisms are among the top-upregulated lipid metabolic pathways, while glycolysis is dysregulated. Seahorse real-time ATP rate analysis revealed a significant decrease in ATP production from the glycolysis pathway in HYP-treated cancer cells. On the other hand, genetic information processes including gene transcription and protein translation were downregulated. Collectively, our results highlight the contribution of HYP to cancer cell metastasis through the PI3K/AKT pathway. Consequently, manipulating HYP release could serve as a therapeutic target for the management of breast cancer.
转移是乳腺癌女性患者的主要死因，乳腺癌是最常见的恶性疾病之一。最近，我们发现次黄嘌呤（HYP）在癌细胞中具有重要的转移作用。HYP是一种天然存在的嘌呤衍生物，通过核苷酸补救途径积极参与核酸的合成。为了更深入地了解HYP的转移机制，在用HYP处理MCF-7细胞后进行了综合转录组学和代谢组学研究。HYP显著激活PI3K/AKT通路，这是癌症转移的一个标志。甘油脂质和脂肪酸代谢是上调最明显的脂质代谢途径，而糖酵解则失调。海马实时ATP速率分析显示，HYP处理的癌细胞中糖酵解途径产生的ATP显著减少。另一方面，包括基因转录和蛋白质翻译在内的遗传信息过程被下调。总的来说，我们的结果突出了HYP通过PI3K/AKT通路对癌细胞转移的作用。因此，控制HYP的释放可作为乳腺癌治疗的一个靶点。
