Jia Shuqin, Qu Tingting, Feng Mengmeng, Ji Ke, Li Ziyu, Jiang Wenguo, Ji Jiafu
1 Laboratory of Surgery, The Affiliated Hospital, Inner Mongolia Medical University, Hohhot, China.
2 Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Tumour Biol. 2017 Jun;39(6):1010428317699755. doi: 10.1177/1010428317699755.
Wnt1-inducible signaling pathway protein-1 is a cysteine-rich protein that belongs to the CCN family, which has been implicated in mediating the occurrence and progression through distinct molecular mechanisms in several tumor types. However, the association of Wnt1-inducible signaling pathway protein-1 with gastric cancer and the related molecular mechanisms remain to be elucidated. Therefore, this study aimed to clarify the biological role of Wnt1-inducible signaling pathway protein-1 in the proliferation, migration, and invasion in gastric cancer cells and further investigated the associated molecular mechanism on these biological functions. We first detected the expression level of Wnt1-inducible signaling pathway protein-1 in gastric cancer, and the reverse transcription polymerase chain reaction have shown that Wnt1-inducible signaling pathway protein-1 expression levels were upregulated in gastric cancer tissues. The expression of Wnt1-inducible signaling pathway protein-1 in gastric cancer cell lines was also detected by quantitative real-time polymerase chain reaction and Western blotting. Furthermore, two gastric cancer cell lines with high expression of Wnt1-inducible signaling pathway protein-1 were selected to explore the biological function of Wnt1-inducible signaling pathway protein-1 in gastric cancer. Function assays indicated that knockdown of Wnt1-inducible signaling pathway protein-1 suppressed cell proliferation, migration, and invasion in BGC-823 and AGS gastric cancer cells. Further investigation of mechanisms suggested that cyclinD1 was identified as one of Wnt1-inducible signaling pathway protein-1 related genes to accelerate proliferation in gastric cancer cells. In addition, one pathway of Wnt1-inducible signaling pathway protein-1 induced migration and invasion was mainly through the enhancement of epithelial-to-mesenchymal transition progression. Taken together, our findings presented the first evidence that Wnt1-inducible signaling pathway protein-1 was upregulated in gastric cancer and acted as an oncogene by promoting proliferation, migration, and invasion in gastric cancer cells.
Wnt1诱导信号通路蛋白-1是一种富含半胱氨酸的蛋白，属于CCN家族，该家族已被证实通过不同分子机制在多种肿瘤类型中介导肿瘤的发生和进展。然而，Wnt1诱导信号通路蛋白-1与胃癌的关联及其相关分子机制仍有待阐明。因此，本研究旨在明确Wnt1诱导信号通路蛋白-1在胃癌细胞增殖、迁移和侵袭中的生物学作用，并进一步探究其在这些生物学功能上的相关分子机制。我们首先检测了胃癌中Wnt1诱导信号通路蛋白-1的表达水平，逆转录聚合酶链反应结果显示，Wnt1诱导信号通路蛋白-1在胃癌组织中的表达水平上调。同时，通过定量实时聚合酶链反应和蛋白质免疫印迹法检测了Wnt1诱导信号通路蛋白-1在胃癌细胞系中的表达。此外，选择两个Wnt1诱导信号通路蛋白-1高表达的胃癌细胞系，以探究Wnt1诱导信号通路蛋白-1在胃癌中的生物学功能。功能实验表明，敲低Wnt1诱导信号通路蛋白-1可抑制BGC-823和AGS胃癌细胞的增殖、迁移和侵袭。机制研究进一步表明，细胞周期蛋白D1被确定为Wnt1诱导信号通路蛋白-1相关基因之一，可促进胃癌细胞增殖。此外，Wnt1诱导信号通路蛋白-1诱导迁移和侵袭的一条途径主要是通过增强上皮-间质转化进程。综上所述，我们的研究首次证实Wnt1诱导信号通路蛋白-1在胃癌中上调，并通过促进胃癌细胞的增殖、迁移和侵袭发挥癌基因作用。
