Zeng Rui, Lin Zhihao, Feng Feiyan, Li Yanyan, Liu Weiwei, He Wenting, Huang Yongjun, Lin Xingtao, Mei Yan, Wu Hongmei, Zhang Qingling
School of Medicine, South China University of Technology, Guangzhou 510006, China.
Department of Pathology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Guangzhou 510080, China.
iScience. 2025 Mar 27;28(5):112296. doi: 10.1016/j.isci.2025.112296. eCollection 2025 May 16.
Cellular metabolic reprogramming supports tumor proliferation, invasion, and metastasis by enhancing resistance to stress and immune clearance. Understanding these metabolic changes within the tumor microenvironment is vital to developing effective therapies. We conducted single-cell RNA sequencing on 11 gastric cancer (GC) samples and eight metastatic lesions, analyzing 92,842 cells across eight cell types, including cancer cells, stromal cells, and immune cells. Our findings highlight that the mitochondrial ATP synthase subunit ATP5MC2 uniquely alters during early GC metastasis. Experiments and clinical data confirmed that ATP5MC2 upregulation facilitates cancer cell proliferation, invasion, and metastasis. Constructing a single-cell atlas revealed significant immune cell heterogeneity associated with GC metastasis and its molecular subtypes. This study underscores the role of ATP5MC2-driven metabolic changes and diverse immune landscapes in promoting GC metastasis, offering new avenues for anti-metastatic treatment development.
细胞代谢重编程通过增强对应激和免疫清除的抗性来支持肿瘤增殖、侵袭和转移。了解肿瘤微环境中的这些代谢变化对于开发有效的治疗方法至关重要。我们对11个胃癌（GC）样本和8个转移病灶进行了单细胞RNA测序，分析了包括癌细胞、基质细胞和免疫细胞在内的8种细胞类型中的92,842个细胞。我们的研究结果突出表明，线粒体ATP合酶亚基ATP5MC2在早期GC转移过程中发生独特改变。实验和临床数据证实，ATP5MC2的上调促进癌细胞增殖、侵袭和转移。构建单细胞图谱揭示了与GC转移及其分子亚型相关的显著免疫细胞异质性。本研究强调了ATP5MC2驱动的代谢变化和多样的免疫格局在促进GC转移中的作用，为抗转移治疗的开发提供了新途径。
