Gastric cancer is one of the most common gastrointestinal malignancy with high mortality in East Asia. Investigation of pathogenic mechanisms of gastric cancer is crucial to develop novel therapeutic strategies and identify new therapeutic candidates. Brain-type glycogen phosphorylase is a glycogen phosphorylase involved in glycogen metabolism, which participates in multiple physiological and pathological processes. Overexpression of brain-type glycogen phosphorylase has been reported in various types of cancer, such as colorectal cancer and non-small cell lung cancer, however, the potential role of brain-type glycogen phosphorylase in gastric cancer remains unclear. Herein, we observed brain-type glycogen phosphorylase expression was significantly elevated in human gastric cancer tissues and positively correlated with the clinical-pathological features including tumor size, lymph node involvement, and tumor, node, metastasis stage of patients with gastric cancer. We further reported brain-type glycogen phosphorylase depletion suppressed the growth of gastric cancer, weakened the epithelial-mesenchymal transformation, and reduced the migration and invasion ability in cell models. We further confirmed brain-type glycogen phosphorylase depletion inhibited tumor growth and lung metastasis in mice. Importantly, we found brain-type glycogen phosphorylase regulated the progression of gastric cancer via Wnt/β-catenin pathway, shedding lights on brain-type glycogen phosphorylase as a promising therapeutic target for drug design and development targeting gastric cancer.
Keywords: brain-type glycogen phosphorylase (PYGB); epithelial–mesenchymal transformation (EMT); gastric cancer (GC); invasion; migration; proliferation.