Multiple Functions of Ten-eleven Translocation 1 during Tumorigenesis

Objective: Aberrant expression of ten-eleven translocation 1 (TET1) plays a critical role in tumor development and progression. We systematically summarized the latest research progress on the role and mechanisms of TET1 in cancer biology. Data Sources: Relevant articles published in English from 1980 to April 2016 were selected from the PubMed database. The terms "ten-eleven translocation 1," " 5mC," " 5hmC," " microRNA," " hypoxia," and " embryonic stem cell" were used for the search. Study Selection: Articles focusing on the role and mechanism of TET1 in tumor were reviewed, including clinical and basic research articles. Results: TET proteins, the key enzymes converting 5-methylcytosine to 5-hydroxymethylcytosine, play vital roles in DNA demethylation regulation. Recent studies have shown that loss of TET 1 is associated with tumorigenesis and can be used as a potential biomarker for cancer therapy, which indicates that TET 1 serves as tumor suppressor gene. Moreover, besides its dioxygenase activity, TET 1 could induce epithelial-mesenchymal transition and act as a coactivator to regulate gene transcription, such as developmental regulator in embryonic stem cells (ESCs) and hypoxia-responsive gene in cancer. The regulation of TET I is also correlated with microRNA in a posttranscriptional modification process. Hence, it is complex but critical to comprehend the mechanisms of TET1 in the biology of ESCs and cancer. Conclusions: TET 1 not only serves as a demethylation enzyme but also plays multiple roles during tumorigenesis and progression. More studies should be carried out to elucidate the exact mechanisms of TET 1 and its associations with cancer before considering it as a therapeutic tool.