Department of Gastrointestinal Anorectal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing City, China.
Department of General Surgery, Xiangya Hospital Central South University, Changsha City, Hunan Province, China.
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820926592. doi: 10.1177/1533033820926592.
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胃肠道恶性肿瘤之一，死亡率很高。研究胃癌的发病机制对于开发新的治疗策略和确定新的治疗靶点至关重要。脑型糖原磷酸化酶是一种参与糖原代谢的糖原磷酸化酶，参与多种生理和病理过程。脑型糖原磷酸化酶的过表达已在多种类型的癌症中被报道，如结直肠癌和非小细胞肺癌，但脑型糖原磷酸化酶在胃癌中的潜在作用尚不清楚。在此，我们观察到脑型糖原磷酸化酶在人胃癌组织中的表达显著升高，并且与包括肿瘤大小、淋巴结受累和胃癌患者的肿瘤、淋巴结、转移分期在内的临床病理特征呈正相关。我们进一步报道，脑型糖原磷酸化酶耗竭抑制了胃癌的生长，减弱了上皮-间充质转化，并降低了细胞模型中的迁移和侵袭能力。我们进一步证实脑型糖原磷酸化酶耗竭抑制了小鼠肿瘤生长和肺转移。重要的是，我们发现脑型糖原磷酸化酶通过 Wnt/β-catenin 通路调节胃癌的进展，为靶向胃癌的药物设计和开发提供了有前途的治疗靶点。
