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.

Keywords: Breast cancer; Hypoxanthine; Metabolomics; Metastasis; Transcriptomics.

© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

转移是乳腺癌患者主要的致死原因，而乳腺癌是常见的恶性疾病之一。最近，我们发现次黄嘌呤（HYP）在癌细胞中的显著转移作用。HYP是一种天然存在的嘌呤衍生物，在核苷酸补救途径中积极参与核酸合成。为了深入了解HYP的转移机制，我们在用HYP处理MCF-7细胞后进行了整合转录组学和代谢组学研究。HYP显著激活了PI3K/AKT通路，这是癌症转移的一个标志性特征。甘油酯和脂肪酸代谢是上调最明显的脂质代谢途径之一，而糖酵解则出现失调。通过使用Seahorse实时ATP速率分析发现，在用HYP处理后的癌细胞中，来自糖酵解路径的ATP生成显著减少。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，我们的结果强调了HYP通过PI3K/AKT通路促进癌细胞转移的作用。因此，调控HYP释放可能可以作为治疗乳腺癌的一个靶点。

关键词：
乳腺癌；次黄嘌呤；代谢组学；转移；转录组学。

© 2025. 作者保留独家授权Springer Science+Business Media, LLC（隶属于Springer Nature）的权利。