Fan Liangsheng, Wang Hongyan, Xia Xi, Rao Yumei, Ma Xiangyi, Ma Ding, Wu Peng, Chen Gang
Cancer Biology Medical Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030;
Oncol Lett. 2012 Dec;4(6):1225-1233. doi: 10.3892/ol.2012.934. Epub 2012 Sep 21.
E-cadherin is a key cell-to-cell adhesion molecule associated with the invasion and metastasis of tumor cells; however, the molecular mechanisms are not entirely understood. In this study, we investigated whether downregulation of E-cadherin by E-cadherin-specific small intefering RNA (siRNA) was able to promote malignant phenotypes of prostate cancer cells through upregulating the metastasis-associated gene 1 (MTA1) in vitro. The expression levels of E-cadherin in human paired prostate adenocarcinoma cell lines, PC-3M-2B4 (2B4) and PC-3M-1E8 (1E8), were investigated using western blot analysis. The alteration of malignant phenotypes associated with decreasing E-cadherin expression were assessed in 2B4 cells using wound-healing assays, solid-phase adhesion assays, invasion assays and cytoskeletal staining. The expression of E-cadherin and MTA1 in normal, localized and metastatic prostate cancer cells was analyzed using immunohistochemistry. Downregulation of E-cadherin using an RNA interference approach led to the upregulation of MTA1 expression, decreased tumor cell adhesion ability as well as enhanced cell mobility, invasion and cellular polarity compared with the controls (P<0.05). E-cadherin regulated MTA1 in a time-dependent manner. The correlation between E-cadherin and MTA1 was inversed in the prostate cancer group (P<0.05; r(s)=-0.434). The data suggest that E-cadherin plays an important role in prostate cancer metastasis, which is likely to be due to the regulation of MTA1 expression. E-cadherin may combine with MTA1 and alter the malignant phenotype of prostate cancer cells. A combined testing strategy for detecting MTA1 and E-cadherin may be sufficient for selecting high-risk patients with metastasis. Therefore, E-cadherin and MTA1 may be potential powerful factors for the treatment of various types of cancer.
E-钙黏蛋白是一种与肿瘤细胞侵袭和转移相关的关键细胞间黏附分子；然而，其分子机制尚未完全明确。在本研究中，我们调查了通过E-钙黏蛋白特异性小干扰RNA（siRNA）下调E-钙黏蛋白是否能够在体外通过上调转移相关基因1（MTA1）来促进前列腺癌细胞的恶性表型。使用蛋白质免疫印迹分析研究了人配对前列腺腺癌细胞系PC-3M-2B4（2B4）和PC-3M-1E8（1E8）中E-钙黏蛋白的表达水平。使用伤口愈合试验、固相黏附试验、侵袭试验和细胞骨架染色评估了2B4细胞中与E-钙黏蛋白表达降低相关的恶性表型改变。使用免疫组织化学分析了正常、局限性和转移性前列腺癌细胞中E-钙黏蛋白和MTA1的表达。与对照组相比，使用RNA干扰方法下调E-钙黏蛋白导致MTA1表达上调、肿瘤细胞黏附能力降低以及细胞迁移、侵袭和细胞极性增强（P<0.05）。E-钙黏蛋白以时间依赖性方式调节MTA1。在前列腺癌组中，E-钙黏蛋白与MTA1之间的相关性呈负相关（P<0.05；r(s)=-0.434）。数据表明，E-钙黏蛋白在前列腺癌转移中起重要作用，这可能是由于对MTA1表达的调节。E-钙黏蛋白可能与MTA1结合并改变前列腺癌细胞的恶性表型。检测MTA1和E-钙黏蛋白的联合检测策略可能足以筛选出具有转移风险的高危患者。因此，E-钙黏蛋白和MTA1可能是治疗各种类型癌症的潜在有力因素。
