MAEL expression links epithelial-mesenchymal transition and stem cell properties in colorectal cancer

被引:22
作者
Li, Qingguo [1 ,2 ]
Wei, Ping [2 ,3 ]
Huang, Ben [1 ,2 ]
Xu, Ye [1 ,2 ]
Li, Xinxiang [1 ,2 ]
Li, Yaqi [1 ,2 ]
Cai, Sanjun [1 ,2 ]
Li, Dawei [1 ,2 ]
机构
[1] Fudan Univ, Dept Colorectal Surg, Shanghai Canc Ctr, Shanghai 200032, Peoples R China
[2] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China
[3] Fudan Univ, Dept Pathol, Shanghai Canc Ctr, Shanghai 200032, Peoples R China
基金
美国国家科学基金会;
关键词
MAEL; colorectal cancer; epithelial-mesenchymal transition; stemness; TRANSCRIPTION FACTOR SNAIL; COLON-CANCER; MAELSTROM; METASTASIS; PATHWAY;
D O I
10.1002/ijc.30388
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MAEL plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilisation, however, its role on cancers is unclear. In this study, MAEL expression was analysed in a tissue microarray containing 185 samples of primary colon cancer tumor samples and human colon cancer cell lines. The effect of MAEL on cell proliferation, tumorigenesis, metastasis and drug resistance was examined in vitro and in vivo. Immunoprecipitation assay, confocal immunofluorescent analysis and luciferase assay were used for mechanism study. As results, MAEL was significantly upregulated in colon cancer patient tissue samples, and elevated MAEL protein levels positively correlated with overall survival and disease free survival of colon cancer patients. Using in vitro and in vivo models, we demonstrated that MAEL expression was correlated with cell proliferation, invasion and drug resistance of colon cancer cells by inducing epithelial-mesenchymal transition and stemness characteristics. Mechanistically, our study demonstrated that MAEL interacts with Snail and inhibit E-cadherin promoter activity. Collectively, MAEL is an oncogene that plays an important role in the development and progression of colon cancer, which may be a novel potential therapeutic target for colon cancer. What's new? The MAEL protein plays a central role in germline integrity and is normally only detected in the testis. MAEL is also abnormally expressed in various cancer tissues and cell lines; however, its role remains controversial. This study found that MAEL was frequently up-regulated in colorectal cancer and may serve as a biomarker for prognosis. In in vitro and in vivo models, MAEL expression was correlated with cell proliferation, invasion and drug resistance of colon cancer cells by inducing the epithelial-mesenchymal transition (EMT) and stemness characteristics. The authors also demonstrated that, mechanistically, MAEL interacts with Snail and inhibit E-cadherin promoter activity.
引用
收藏
页码:2502 / 2511
页数:10
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