Department of Cardiothoracic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Lab Invest. 2011 May;91(5):778-87. doi: 10.1038/labinvest.2011.12. Epub 2011 Feb 21.
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.
食管鳞状细胞癌（ESCC）是最致命的恶性肿瘤之一，因为它具有很高的转移频率。鉴于 MUC1 与 ESCC 和肿瘤转移的关联，我们探讨了 MUC1 在 ESCC 转移中的潜在作用。在 40 例 ESCC 和 20 对配对正常组织标本中，我们发现 MUC1 在 ESCC 中的表达显著增加，更重要的是，在有淋巴结转移的患者中，MUC1 和 MMP13 的表达强烈相关。细胞模型研究表明，MUC1 的过表达上调了 MMP13 的表达，导致细胞迁移增加。支持转录调控模式，启动子分析表明 MUC1 通过 Runx-2 结合位点刺激 MMP13 表达。通过发现耗尽 MUC1 会导致 MMP13 和细胞迁移、侵袭和黏附的表达减少，进一步证实了 MUC1 与细胞迁移的联系。此外，过表达 MMP13 完全挽救了细胞转移潜力的丧失。总之，我们的研究结果表明，MUC1 通过刺激 MMP13 的表达促进 ESCC 转移，提示 MUC1 可作为 ESCC 的一种新型诊断生物标志物和治疗靶点。
