CMTM3 inhibits cell migration and invasion and correlates with favorable prognosis in gastric cancer.
Bottom Line: Restoration of CMTM3 significantly affected migration and invasion of AGS and SGC-7901 cells (P < 0.001).In vivo experiments showed that peritoneal disseminated metastases were significantly suppressed by CMTM3 (P < 0.001).We further showed that the expression of MMP2 and the phosphorylation of Erk1/2 were decreased when CMTM3 was restored.
Affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University Center for Human Disease Genomics, Beijing, China; Key Laboratory of Medical Immunology, Ministry of Health, Beijing, China.Show MeSH
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Mentions: Our previous study showed that CMTM3 was silenced or downregulated in carcinoma cell lines with regulatory region methylation.6 In this study, we chose gastric cancer cell lines that have been widely used in gastric cancer research, especially in functional studies. We examined the expression of CMTM3 in nine cell lines by RT-PCR at the mRNA level. The result showed that CMTM3 was silenced in four of these cell lines (Fig.1a). Then we carried out real-time PCR and Western blot analyses to confirm the expression of CMTM3. As shown in Figure1(a), SGC-7901 had the highest mRNA level of CMTM3, and CMTM3 protein could be only detected in SGC-7901 by Western blotting (Fig.1a). To analyze the methylation status of CMTM3, methylation-specific PCR was carried out in nine cell lines. Full or partial methylation was found in the six of these (Fig.1a). Furthermore, we treated AGS, SNU1, SNU16 and KATOIII cells with demethylating agent Aza, or combined with histone deacetylase inhibitor trichostatin A (TSA). Indeed, CMTM3 expression was restored by Aza and TSA both on mRNA and protein levels (Fig.1b). However, in SNU16 cells, the expression of CMTM3 was not fully restored when treated with Aza. This result indicates that histone acetylation might play a more important role in controlling CMTM3 expression in SNU16 cells. These findings are consistent with our previous results, and indicate that epigenetic changes are correlated to CMTM3 silencing in gastric cancer cell lines.
Affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University Center for Human Disease Genomics, Beijing, China; Key Laboratory of Medical Immunology, Ministry of Health, Beijing, China.