Progress of estrogen receptor and splice variants in ovarian carcinoma

Ovarian cancer is a typical estrogen-dependent tumor, with its initiation and progression closely associated with estrogen regulation. Estrogen exerts physiological effects by binding to estrogen receptors (ERs), and aberrant activation of ER signaling pathways is a crucial mechanism in the pathogenesis of ovarian cancer. ERα promotes ovarian cancer cell proliferation and migration, and is linked to cisplatin resistance, while its splice variants modulate cancer cell sensitivity to tamoxifen. Conversely, ERβ functions as a tumor suppressor and counteracts the pro-tumorigenic effects of ERα. Distinct ERβ subtypes have divergent biological functions, and their agonists can enhance cancer cell chemosensitivity. G protein-coupled estrogen receptor 1 (GPER1), a membrane estrogen receptor, mediates the non-genomic effects of estrogen. Its role depends on clinical stages and subcellular localization, and its association with ovarian cancer prognosis is under debate. GPER1 may interact with ERα in ovarian cancer, yet the specific crosstalk mechanism remains unelucidated. Elucidating the complex functional crosstalk of estrogen and ERs, as well as the diverse roles of ER splice variants, is expected to provide novel insights for the early diagnosis and identification of therapeutic targets for ovarian cancer.