DNMT1 ablation suppresses tumorigenesis by inhibiting the self-renewal of esophageal cancer stem cells
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Ying Teng1,2, Xiying Yu1,2, Hui Yuan1,2, Liping Guo1,2, Wei Jiang1 and Shih-Hsin Lu1,2,3
1Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China
3Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Shih-Hsin Lu, email: firstname.lastname@example.org
Wei Jiang, email: email@example.com
Keywords: cancer stem cells; esophageal cancer; ESCC; DNMT1; 5-aza-dC
Received: July 12, 2017 Accepted: December 01, 2017 Epub: January 02, 2018 Published: April 10, 2018
Cancer stem cells (CSCs) have been isolated from many tumors and considered as the main reason of cancer recurrence and metastasis. DNA methyltransferase 1 (DNMT1) mediates DNA methylation and plays an important role in CSCs maintenance. However, the function of DNMT1 in CSCs of esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we examined the role of DNMT1 in regulating self-renewal in CSCs of ESCC. We found a high expression of DNMT1 in both side population (SP) cells and sphere formation cells that represented as substitutes for CSCs in KYSE150 and EC109 ESCC cell lines. We performed the knockdown of DNMT1 using lentivirus-mediated RNA interference (RNAi) methods. We revealed that ablation of DNMT1 resulted in the numbers and self-renewal abilities of CSCs refrained significantly in ESCC cells. As a result of the CSCs inhibition, the malignant phenotypes such as cell proliferation, colony formation, migration and drug resistance abilities were dramatically inhibited in ESCC cells. Treatment of 5-aza-2'-deoxycytidine (5-aza-dC), a DNMT inhibitor, also resulted in the inhibition of CSCs and malignant profiles in ESCC cells. Our findings also provided the first evidence that 5-aza-dC inhibited the colony and sphere formation of CSCs. Thus, our results indicated that DNMT1 was important for the self-renewal maintenance of CSCs in ESCC, and 5-aza-dC could be a potential therapy for the CSCs of ESCC.
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