SKA2 promotes gastric cancer progression by regulating glutathione metabolism

The role of spindle and kinetochore-associated complex subunit 2 (SKA2) in gastric cancer (GC) pathogenesis remains largely undefined. Here, we report that SKA2 is overexpressed in GC and correlates with poor prognosis. Functionally, SKA2 silencing inhibits tumor growth, induces G2/M arrest, and promotes apoptosis both <i>in vitro</i> and <i>in vivo</i>. Mechanistically, SKA2 upregulates the glycine transporter SLC6A9, enhancing glycine uptake and glutathione (GSH) synthesis to maintain redox homeostasis. Consequently, SKA2 depletion disrupts this metabolic balance, leading to reactive oxygen species (ROS) accumulation and DNA damage. This oxidative stress activates the ATM/Chk2 pathway to trigger cell-cycle arrest and the ATM/JNK pathway to induce apoptosis. Our findings identify SKA2 as a critical driver of metabolic reprogramming that shields GC cells from oxidative stress-induced death, highlighting the SKA2-SLC6A9-GSH-ROS axis as a promising therapeutic target.