Mechanism and biological significance of the overexpression of IFITM3 in gastric cancer
Mechanism and biological significance of the overexpression of IFITM3 in gastric cancer
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DOI：
10.3892/or.2014.3522
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发表时间：
2014-12-01
期刊：
影响因子：
4.2
通讯作者：
Sun, Yueming
中科院分区：
文献类型：
--
作者：
Hu, Jun;Wang, Shuwei;Sun, Yueming
干扰素诱导的跨膜蛋白3（IFITM 3）是一种潜在的分子标记物。据报道，IFITM 3在各种人类疾病中上调，包括结肠癌和乳腺癌、星形细胞瘤以及溃疡性结肠炎。然而，IFITM 3在胃癌（GC）中表达失调的临床意义和潜在机制仍有待确定。本研究旨在检测IFITM 3在人胃癌细胞和标本中的表达，探讨IFITM 3基因敲减对胃癌生长的调控作用及其可能机制。RT-qPCR、Western blot和免疫组化检测结果显示，IFITM 3在胃癌细胞系和胃癌组织中的表达均高于相应的正常对照组，且与胃癌分化程度、淋巴结转移、远处转移及肿瘤淋巴结转移分期密切相关。此外，IFITM 3表达的敲低在体外显著抑制肿瘤细胞的迁移、侵袭和增殖，将肿瘤细胞阻滞在G 0/G1期，并减少细胞周期中S期的细胞数量。我们初步证实IFITM 3可以通过Wnt/beta-catenin信号通路的活性来介导。进一步的研究表明，IFITM 3的沉默有效地逆转了上皮-间充质转化（EMT）表型，并降低了MMP-2和MMP-9表达的活性。总之，这些数据表明IFITM 3是GC的潜在治疗靶点。
Interferon-induced transmembrane protein 3 (IFITM3) has been recently identified as a potential molecular marker. IFITM3 has been reported to be upregulated in various human diseases, including colon and breast cancer, astrocytoma, as well as ulcerative colitis. However, the clinical significance and underlying mechanisms of IFITM3 dysregulated expression in gastric cancer (GC) remain to be determined. The present study aimed to evaluate the expression of IFITM3 in human gastric tumor cells and specimens and investigate the effects of IFITM3 knockdown in the regulation of GC growth and its potential mechanism. IFITM3 expression was significantly overexpressed in the GC cell lines and GC tissues compared with corresponding normal controls by RT-qPCR, western blot analysis and immunohistochemistry, and this overexpression was correlated with tumor differentiation, lymph node and distant metastasis, and advanced tumor node metastasis stages. Furthermore, knockdown of IFITM3 expression suppressed tumor cell migration, invasion and proliferation significantly in vitro, arrested tumor cells at the G0/G1 phase and reduced the cell numbers in the S phase of the cell cycle. We preliminarily confirmed that IFITM3 can be mediated by the activities of Wnt/beta-catenin signaling. Further investigation revealed that silencing of IFITM3 effectively reversed the epithelial-to-mesenchymal transition (EMT) phenotype and reduced the activities of MMP-2 and MMP-9 expression. Taken together, these data suggested that IFITM3 is a potential therapeutic target for GC.