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The oncogenic transcription factor ZNF217 orchestrates several molecular signaling networks to reprogram integrated circuits governing hallmark capabilities within cancer cells. High levels of ZNF217 expression provide advantages to a specific subset of cancer cells to reprogram tumor progression, drug resistance and cancer cell plasticity. ZNF217 expression level, thus, provides a powerful biomarker of poor prognosis and a predictive biomarker for anticancer therapies. Cancer epigenetic mechanisms are well known to support the acquisition of hallmark characteristics during oncogenesis. However, the complex interactions between ZNF217 and epigenetic processes have been poorly appreciated. Deregulated DNA methylation status at ZNF217 locus or an intricate cross-talk between ZNF217 and noncoding RNA networks could explain aberrant ZNF217 expression levels in a cancer cell context. On the other hand, the ZNF217 protein controls gene expression signatures and molecular signaling for tumor progression by tuning DNA methylation status at key promoters by interfering with noncoding RNAs or by refining the epitranscriptome. Altogether, this review focuses on the recent advances in the understanding of ZNF217 collaboration with epigenetics processes to orchestrate oncogenesis. We also discuss the exciting burgeoning translational medicine and candidate therapeutic strategies emerging from those recent findings connecting ZNF217 to epigenetic deregulation in cancer.

International audience; Breast cancer (BC) is one of the most common cancers in women worldwide. Even though the role of estrogen receptor alpha (ERα) is extensively documented in the development of breast tumors, other members of the nuclear receptor family have emerged as important players. Synthetic glucocorticoids (GCs) such as dexamethasone (dex) are commonly used in BC for their antiemetic, anti-inflammatory, as well as energy and appetite stimulating properties, and to manage the side effects of chemotherapy. However, dex triggers different effects depending on the BC subtype. The glucocorticoid receptor (GR) is also an important marker in BC, as high GR expression is correlated with a poor and good prognosis in ERα-negative and ERα-positive BCs, respectively. Indeed, though it drives the expression of pro-tumorigenic genes in ERα-negative BCs and is involved in resistance to chemotherapy and metastasis formation, dex inhibits estrogen-mediated cell proliferation in ERα-positive BCs. Recently, a new natural ligand for GR called OCDO was identified. OCDO is a cholesterol metabolite with oncogenic properties, triggering mammary cell proliferation in vitro and in vivo. In this review, we summarize recent data on GR signaling and its involvement in tumoral breast tissue, via its different ligands.