title: MUC1 induces metastasis in esophageal squamous cell carcinoma by upregulating matrix metalloproteinase 13.
abstract: 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.
authors.affiliation: Department of Cardiothoracic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yan
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Liao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Jiening
authors.initials: J
authors.lastname: Sun
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawano
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Wang
authors.forename: Ziang
authors.initials: Z
authors.lastname: Cao
authors.forename: Zhugang
authors.initials: Z
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
mesh_terms: D000818:Animals; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002460:Cell Line; D017931:DNA Primers; D004938:Esophageal Neoplasms / Q000473:pathology*; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D018396:Mucin-1 / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D051381:Rats; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D017931:DNA Primers; D018396:Mucin-1; D053509:Matrix Metalloproteinase 13