Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, Nanyang, China.
Henan Key Laboratory of Zhang Zhongjing Formulae and Herbs for Immunoregulation, Nanyang Institute of Technology, Nanyang, China.
Cancer Med. 2019 May;8(5):2360-2371. doi: 10.1002/cam4.2078. Epub 2019 Mar 13.
Esophageal cancer is one of the most common tumor in the world, and the morbidity rate is as high as 100/100 000 in some parts of China. Therefore, it is important and urgent to explore the pathogenesis of esophageal cancer and find new therapeutic targets for esophageal cancer. In this study, we found that a novel tumor suppressor SPINK5 is significantly reduced in the development of esophageal cancer, and is closely related to the pathological differentiation and lymph node metastasis of esophageal cancer via bioinformatics analysis and esophageal cancer tissue array. Further studies have found that SPINK5 is closely related to Wnt/β-catenin signaling pathway by bioinformatics analysis and western blot. In esophageal cancer cells, SPINK5 overexpression can inhibit Wnt/β-catenin signaling pathway. Combined with LiCl or MG-132 treatment, SPINK5 can inhibit GSK3β phosphorylation and promote β-catenin protein degradation, thus inhibit Wnt/β-catenin signaling pathway. In vivo study, SPINK5 overexpression can significantly inhibit the growth of esophageal cancer cells. Our study shows that SPINK5 can inhibit the proliferation, migration, and invasion of esophageal cancer cells by inhibiting Wnt/β-catenin signaling pathway, and thus plays an important role in the development of esophageal cancer, and may serve as a treatment target of esophageal cancer.
食管癌是世界上最常见的肿瘤之一，在中国的某些地区发病率高达 100/100000。因此，探索食管癌的发病机制，寻找新的食管癌治疗靶点非常重要和紧迫。在本研究中，我们发现一种新型肿瘤抑制因子 SPINK5 在食管癌的发生发展中显著下调，通过生物信息学分析和食管癌组织芯片发现其与食管癌的病理分化和淋巴结转移密切相关。进一步研究发现，通过生物信息学分析和 Western blot 发现 SPINK5 与 Wnt/β-catenin 信号通路密切相关。在食管癌细胞中，过表达 SPINK5 可抑制 Wnt/β-catenin 信号通路。联合 LiCl 或 MG-132 处理，SPINK5 可抑制 GSK3β 磷酸化并促进 β-catenin 蛋白降解，从而抑制 Wnt/β-catenin 信号通路。体内研究表明，过表达 SPINK5 可显著抑制食管癌细胞的生长。本研究表明，SPINK5 通过抑制 Wnt/β-catenin 信号通路抑制食管癌细胞的增殖、迁移和侵袭，从而在食管癌的发生发展中发挥重要作用，可能成为食管癌的治疗靶点。
