title: Involvement of S100A14 protein in cell invasion by affecting expression and function of matrix metalloproteinase (MMP)-2 via p53-dependent transcriptional regulation.
abstract: S100 proteins have been implicated in tumorigenesis and metastasis. As a member of S100 proteins, the role of S100A14 in carcinogenesis has not been fully understood. Here, we showed that ectopic overexpression of S100A14 promotes motility and invasiveness of esophageal squamous cell carcinoma cells. We investigated the underlying mechanisms and found that the expression of matrix metalloproteinase (MMP)-2 is obviously increased after S100A14 gene overexpression. Inhibition of MMP2 by a specific MMP2 inhibitor at least partly reversed the invasive phenotype of cells overexpressing S100A14. By serendipity, we found that S100A14 could affect p53 transactivity and stability. Thus, we further investigated whether the effect of MMP2 by S100A14 is dependent on p53. A series of biochemical assays showed that S100A14 requires functional p53 to affect MMP2 transcription, and p53 potently transrepresses the expression of MMP2. Finally, RT-quantitative PCR analysis of human breast cancer specimens showed a significant correlation between S100A14 mRNA expression and MMP2 mRNA expression in cases with wild-type p53 but not in cases with mutant p53. Collectively, our data strongly suggest that S100A14 promotes cell motility and invasiveness by regulating the expression and function of MMP2 in a p53-dependent manner.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Chunpeng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Shouhui
authors.initials: S
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Tong
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: liuzh@cicams.ac.cn.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Liu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C462950:S100A14 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2