MUC1 induces metastasis in esophageal squamous cell carcinoma by upregulating matrix metalloproteinase 13
MUC1 induces metastasis in esophageal squamous cell carcinoma by upregulating matrix metalloproteinase 13
复制标题
MUC1通过上调基质金属蛋白酶13诱导食管鳞状细胞癌转移
DOI：
10.1038/labinvest.2011.12
复制
发表时间：
2011-05-01
影响因子：
5
通讯作者：
Huang, Lei
中科院分区：
文献类型：
--
作者：
Ye, Qing;Yan, Zheng;Huang, Lei
食管鳞状细胞癌（ESCC）是一种易转移的恶性肿瘤。鉴于MUC 1与ESCC和肿瘤转移的相关性，我们探讨了MUC 1在ESCC转移中的潜在作用。在40例ESCC和20例配对正常组织标本中，我们发现MUC 1在ESCC中的表达显著增加，更重要的是，MUC 1和MMP 13的表达在有淋巴结转移的患者中强烈相关。细胞模型的研究表明，MUC 1的过表达上调MMP 13的表达，导致细胞迁移增加。启动子分析显示MUC 1通过Runx-2结合位点刺激MMP 13的表达，这支持了一种转录调控模式。MUC 1与细胞运动性的联系通过MUC 1的缺失导致MMP 13的表达减少以及细胞迁移、侵袭和粘附的发现进一步证实。此外，MMP 13的过表达完全挽救了细胞转移潜力的丧失。总的来说，我们的研究结果表明，MUC 1通过刺激MMP 13的表达，促进ESCC转移，这表明MUC 1作为一种新的诊断生物标志物和治疗ESCC的目标。
Esophagus squamous cell carcinoma (ESCC) is one of the most deadly malignances because of its high frequency of metastasis. Given the associations of MUC1 with ESCC and tumor metastasis, we explored a potential role of MUC1 in ESCC metastasis. Among 40 ESCC and 20 paired normal tissue specimens examined, we found a significant increase of MUC1 expression in ESCC and more importantly, that expression of MUC1 and MMP13 are strongly correlated in patients who had lymph node metastasis. Studies with cell models indicated that overexpression of MUC1 upregulates the expression of MMP13, leading to increased cell migration. In support of a mode of transcriptional regulation, promoter analysis revealed that MUC1 stimulates MMP13 expression through the Runx-2-binding site. The link of MUC1 to cell motility was further confirmed by the finding that depletion of MUC1 resulted in reduced expression of MMP13 and cell migration, invasion and adhesion. Moreover, the loss of cell metastatic potential was rescued by overexpression of MMP13 completely. Collectively, our findings indicate that MUC1 contributes to ESCC metastasis by stimulating MMP13 expression, suggesting MUC1 as a novel diagnostic biomarker and therapeutic target in ESCC.