Metabolic alterations and immune heterogeneity in gastric cancer metastasis.

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.