Figure 2.

HMGA2/TET1/HOXA signalling in breast cancer cells. Depletion of the architectural transcription factor high mobility group AT-hook 2 (HMGA2) induces TET1 (ten–eleven translocation methylcytosine dioxygenases). This molecule initiates demethylation of DNA and is associated with tumorigenesis in many cancers. TET1 binds and demethylates its own promoter and the promoters of HOXA7 and HOXA9, increasing their expression, which may result in the inhibition of breast cancer growth and metastasis, already demonstrated for HOXA9 using mouse xenografts [35]. The demethylation promoted by TET1 allows the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and this to 5-formylcytosine (5fC), which in turn is converted in to 5-carboxycytosine (5caC) and at the end in an unmodified cytosine (C).