We previously have demonstrated that, in estrogen receptor positive (ER+) breast cancer cells, the nuclear PADI2 targets histone H3R26 for citrullination and specifically facilitates ER binding by modifying nucleosome structure. However, the role of cytoplasmic PADI2 (major form PADI2 in cells) in estrogen signaling is still unclear.
There are two ER subtypes, ERa and ERb, that belong to the nuclear receptor family, once activated by estrogen, have different biological functions as they may regulate different targets.
ERa is frequently detected in the early development of breast cancer tissues and is associated with a poor prognosis and an increased proliferation rate, while the presence of ERb indicates better survival and is generally regarded as an anti-tumor factor. Changes in the ratio of ERa/ERb protein levels determine the balance between cell proliferation and apoptosis. Here, we will discuss the novel role of cytoplasmic PADI2 in regulation of ratio of ERa/ERb protein levels in breast cancer cells. Eventually, PADI2 inhibitors combined with endocrine therapy drugs for breast cancer may help retard or prevent the occurrence of endocrine therapy resistance for ER+ breast cancers.