Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Cancer Biol Ther. 2013 Mar;14(3):262-70. doi: 10.4161/cbt.23299. Epub 2013 Jan 8.
Cadherin-17 (CDH17), as a structurally unique member of the cadherin superfamily, has been identified to predict a poor prognosis for gastric cancer (GC). Our previous study demonstrated the positive correlation between CDH17 and lymph node micrometastasis in GC. We sought to further identify the role of CDH17 in the tumorigenesis and lymphatic metastasis of GC. Hence, we inhibited the CDH17 expression in MKN-45 gastric cancer cells by using RNA interference. Consequently, the malignant potency of cancer cells was evaluated, and the change in NFκB signaling pathway was also probed. Tumor growth and lymphatic metastasis model were conducted in nude mice to confirm the hypothesis. Downregulation of CDH17 not only suppressed the proliferation, adherence and invasion potency of MKN-45 cells, but also induced cell cycle arrest. Meanwhile, the NFκB signaling pathway was inactivated as well, with the reductions of downstream proteins including VEGF-C and MMP-9. Moreover, silencing CDH17 inhibited tumor growth in vivo significantly, and there was no lymph node metastasis detected in the mice without CDH17 expression, as opposed to the positive nodes found in controls. CDH17 is a novel oncogene in gastric cancer cells, which is associated with lymphatic metastasis and proliferation strongly. The inactivation of NFκB signaling pathway might be involved in targeting CDH17 in GC. On the whole, CDH17 is proposed to serve as a biomarker and attractive therapeutic target in GC.
钙黏蛋白 17（CDH17）作为黏附素超家族中结构独特的成员，已被确定可预测胃癌（GC）的预后不良。我们之前的研究表明 CDH17 与 GC 中的淋巴结微转移之间存在正相关。我们试图进一步确定 CDH17 在 GC 发生和淋巴转移中的作用。因此，我们使用 RNA 干扰抑制 MKN-45 胃癌细胞中的 CDH17 表达。随后，评估了癌细胞的恶性潜能，并探究了 NFκB 信号通路的变化。在裸鼠中进行肿瘤生长和淋巴转移模型实验以验证假设。下调 CDH17 不仅抑制了 MKN-45 细胞的增殖、黏附和侵袭能力，还诱导了细胞周期停滞。同时，NFκB 信号通路也被失活，下游蛋白包括 VEGF-C 和 MMP-9 的表达减少。此外，沉默 CDH17 显著抑制体内肿瘤生长，并且在没有 CDH17 表达的小鼠中未检测到淋巴结转移，而在对照组中则发现了阳性淋巴结。CDH17 是胃癌细胞中的一种新型癌基因，与淋巴转移和增殖密切相关。NFκB 信号通路的失活可能参与了 GC 中针对 CDH17 的靶向治疗。总的来说，CDH17 有望作为 GC 的生物标志物和有吸引力的治疗靶点。
