metastasis [72,73]. trans-eQTL identified a SNP less than 35 kb upstream of ZNF639 (SNP_A-1686963) driving expression of the TCF12 gene at 15q21. TCF12, a.k.a. HTF4 or ME1, is a basic helix-loop-helix TF with key roles in development [74]. In a mouse experiment, TCF12 was associated with obesity [14], a key prognostic factor for endometrial cancer [75]. Because the stoichiometric concentration of TFs within the nucleus may control gene expression [43], this association proposes a link between obesity and TCF12 through ZNF639. Because ZNF639 regulates anchoring of E-cadherin to the cytoskeleton through alpha N-catenin [76], given the importance of cell adhesion proteins in cancer [77], future studies of endometrial cancer might focus on ZNF639.
