The AIB1/NCOA3/SRC-3 Oncogene

Abstract

A member of the NCOA/SRC/p160 co-activator family, AIB1 is amplified and overexpressed in multiple cancer types, notably breast, ovarian, and pancreatic cancer. Common to all members of the NCOA/SRC/p160 family are bHLH-PAS, receptor interaction, and CBP/p300 interacting activation domains. The protein acts as a scaffold to support the transcriptional activity of many DNA binding transcription factors, such as the ER, AP-1, E2F, NFκB, and TEADs. In doing so, the multi-domain protein facilitates chromatin remodeling and oncogenic gene transcription. Further, the AIB1Δ4 isoform promotes tumorigenesis and metastasis through interaction with chromatin in the nucleus or at the periphery of the cell. Pathologically, AIB1 promotes the transformation of normal tissue to cancerous lesions in multiple diseases, and loss delays progression. AIB1 has also been implicated in cancer recurrence and pharmacological resistance. We will discuss the structure and isoforms of AIB1, the physiological consequences of its interaction with transcription factors and hormone receptors, and clinical significance of the protein.

Loss of ANCO1 repression at AIB1/YAP targets drives breast cancer progression

“…In normal human breast tissue, AIB1 levels are low, but significantly increase at the DCIS stage of breast cancer [6]. AIB1 functions as a transcription co-activator and has been shown to interact with many transcription factors, such as nuclear receptors, NFjB, and E2F, to promote transcription in physiology and disease contexts [7]. Further, we and others have shown that AIB1 can also recruit transcription repressor proteins, such as the putative tumor suppressor ANCO1/ANKRD11, to suppress transcription at select sites [8][9][10][11], which may also contribute to malignant progression.…”

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

“…AIB1 is known to act as a coactivator for several transcription factors other than the ER. Besides E2F and Ets interactions described above, AIB1 increases the expression of AP-1 (activator protein 1), TEADs and NF-κB (nuclear factor kappa B) dependent target genes, among others (reviewed in 145 ). Briefly, AIB1 coactivation of AP-1 promoted transcription of matrix metalloproteinases and increased invasiveness of human breast cancer cells ( 146 ).…”