[Show abstract][Hide abstract] 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.
Preview · Article · Mar 2012 · Journal of Biological Chemistry
[Show abstract][Hide abstract] ABSTRACT: Reelin (RELN), which is a glycoprotein secreted by Cajal-Retzius cells of the developing cerebral cortex, plays an important role in neuronal migration, but its role in cell migration and cancer metastasis is largely unclear. Here, we showed that cell motility was significantly increased in KYSE-510 cells by TGF-β1 treatment. Moreover, TGF-β1 decreased RELN mRNA expression and overexpression of Reelin at least partly reversed TGF-β1-induced cell migration in KYSE-30 cells. Furthermore, this negative regulation of Reelin expression by TGF-β1 was through Snail, one transcription factor which was induced by TGF-β1 in KYSE-510 cells. RELN promoter activity was reduced in parallel with the induction of Snail after TGF-β1 treatment and Snail suppressed both RELN promoter activity and expression through binding to E-box sequences in the RELN promoter region in ESCC cells. Knockdown of RELN induced cell migration in KYSE-510 cells, together with the increase of mesenchymal markers expression. Taken together, Reelin is an essential negative regulator in the TGF-β1-induced cell migration process, and is suppressed by TGF-β pathway at the transcriptional level through Snail regulation. Therefore, the correlation of Reelin and TGF-β pathway was critical in cancer metastasis, and Reelin could be one potential anti-metastasis target in future clinical practice.
[Show abstract][Hide abstract] ABSTRACT: Arginine methylation of histone H3 and H4 plays important roles in transcriptional regulation in eukaryotes such as yeasts, fruitflies, nematode worms, fish and mammals; however, less is known in plants. In the present paper, we report the identification and characterization of two Arabidopsis thaliana protein arginine N-methyltransferases, AtPRMT1a and AtPRMT1b, which exhibit high homology with human PRMT1. Both AtPRMT1a and AtPRMT1b methylated histone H4, H2A, and myelin basic protein in vitro. Site-directed mutagenesis of the third arginine (R3) on the N-terminus of histone H4 to lysine (H4R3N) completely abolished the methylation of histone H4. When fused to GFP (green fluorescent protein), both methyltransferases localized to the cytoplasm as well as to the nucleus. Consistent with their subcellular distribution, GST (glutathione transferase) pull-down assays revealed an interaction between the two methyltransferases, suggesting that both proteins may act together in a functional unit. In addition, we demonstrated that AtFib2 (Arabidopsis thaliana fibrillarin 2), an RNA methyltransferase, is a potential substrate for AtPRMT1a and AtPRMT1b, and, furthermore, uncovered a direct interaction between the protein methyltransferase and the RNA methyltransferase. Taken together, our findings implicate AtPRMT1a and AtPRMT1b as H4-R3 protein arginine N-methyltransferases in Arabidopsis and may be involved in diverse biological processes inside and outside the nucleus.
Preview · Article · Dec 2007 · Biochemical Journal