AIB1/SRC-3/NCOA3 function in estrogen receptor alpha positive breast cancer

Abstract

The estrogen receptor alpha (ERα) is a steroid receptor that is pivotal in the initiation and progression of most breast cancers. ERα regulates gene transcription through recruitment of essential coregulators, including the steroid receptor coactivator AIB1 (Amplified in Breast Cancer 1). AIB1 itself is an oncogene that is overexpressed in a subset of breast cancers and is known to play a role in tumor progression and resistance to endocrine therapy through multiple mechanisms. Here we review the normal and pathological functions of AIB1 in regard to its ERα-dependent and ERα-independent actions, as well as its genomic conservation and protein evolution. We also outline the efforts to target AIB1 in the treatment of breast cancer.

Potentials and future perspectives of multi-target drugs in cancer treatment: the next generation anti-cancer agents

“…The AIB1 is a known potent transcriptional coactivator of estrogen receptor α that functions through direct contact with the nuclear receptor, and the overexpression (in 48.3% cases) is associated with shortened patient survival and acts as a biomarker for NSCLC patients with poor prognosis [183,192]. The C-MET alterations are also associated with NSCLC's poor prognosis and its expression upregulates in 25-75% of diagnosed cases [193].…”

Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target

“…Post-menopause status, however, modifies the risk conveyed by SRC-3 overexpression, converting it to a positive marker, a predictive marker of tamoxifen benefit [279]. Initially SRC-3 was shown to have a role in the estrogen-dependent proliferation of breast epithelial cells; this was because SRC-3 was implicated in the regulation of estrogen-dependent effects on breast cancer development and progression [17]. However, SRC-3 also affects the growth of hormone-independent breast cancer and SRC-3 levels are limiting for IGF-1-, EGF-, and heregulin-stimulated biological responses in breast cancer cells, and consequently, the PI3 K/Akt/mTOR and other EGFR/HER2 signaling pathways are controlled by changes in SRC-3 protein levels [280].…”

“…SRC-3 has pleiotropic effects in normal physiology, including cell proliferation, survival and metabolism, along with vasoprotection, female reproductive function, and puberty [17]. SRC-3 null mice displayed delayed puberty, slowed mammary gland growth, reproductive malfunction, and dwarfism due to alterations in the IGF-1 (insulin-like growth factor 1) signaling pathway [7,8].…”

“…SRC-3 is also involved in the creation of an immunosuppressive tumor microenvironment and promotes stemness [15,16]. In regard to cancer treatment, SRC-3 is involved in the development of resistance to both endocrine therapy and immunotherapy in patients with BCa [17].…”