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.

胃癌是东亚地区最常见的高死亡率胃肠道恶性肿瘤之一。胃癌的致病机制研究对于开发新的治疗策略和确定新的治疗候选者至关重要。脑型糖原磷酸化酶是一种参与糖原代谢的糖原磷酸化酶，其参与多种生理和病理过程。已经报道了脑型糖原磷酸化酶在多种类型的癌症中的过表达，例如结肠直肠癌和非小细胞肺癌，但是，脑型糖原磷酸化酶在胃癌中的潜在作用仍不清楚。在这里 我们观察到人胃癌组织中脑型糖原磷酸化酶的表达显着升高，并且与胃癌患者的临床病理特征（包括肿瘤大小，淋巴结受累以及肿瘤，淋巴结，转移阶段）呈正相关。我们还报道了脑型糖原磷酸化酶耗竭抑制了胃癌的生长，削弱了上皮-间质转化，并降低了细胞模型的迁移和侵袭能力。我们进一步证实脑型糖原磷酸化酶耗竭抑制小鼠的肿瘤生长和肺转移。重要的是，我们发现脑型糖原磷酸化酶通过Wnt /β-catenin途径调节胃癌的进展，