**6. AIB1 interacts with transcription factors**

Though AIB1 has been primarily studied for its interaction with the Estrogen receptor (see Section 4), AIB1 interacts with a diverse set of transcription factors which may explain its oncogenic role in cancer. We will focus on the interaction of AIB1 with known oncogenic transcription factors to highlight the importance of AIB1 as a transcriptional co-activator across a variety of signaling pathways. As a general pattern, AIB1 acts to potentiate transcription of signaling pathways; when it binds to a transcription factor, it tends to increase the expression of target genes synergistically. Additionally, many pathways simultaneously activate their effectors and act on AIB1 in

**55**

**Figure 2.**

*behavior, and select transcriptional targets (italicized).*

*The AIB1/NCOA3/SRC-3 Oncogene*

**6.1 AP-1**

**6.2 The TEADs**

*DOI: http://dx.doi.org/10.5772/intechopen.80925*

the cytosol to increase nuclear translocation. Thus, many growth factors signaling cascades converge on transcription factors and AIB1. We have selected a few of the most well studied oncogenic transcription factors whose activity is increased by AIB1 in cancer. **Figure 2** illustrates these interactions and their phenotypic consequences.

The activator protein transcription factor is a heteromeric complex consisting of Fos, Jun, ATF, and MAF family members, and can act as an oncogene that drives proliferative signaling. The complexes regulate a large swath of human gene expression and can contribute to both pro- and anti-tumorigenic gene expression (reviewed in [52]). AIB1 uses its C-terminal activation domains to interact with the Fos and Jun family members to activate and potentiate signaling, as measured by synthetic luciferase reporter assays and target gene expression [10]. Clinically, this interaction has been identified to be relevant in driving many pro-proliferative cancer genes. In hormone independent prostate cancer, responsiveness to IGF-Akt signaling by AIB1-AP-1 cooperation synergizes their effects on the transcription of target genes, thereby promoting cell growth and division [53]. In both hormonedependent and -independent breast cancer (in which AIB1 is amplified), AIB1 interaction with and co-activation of AP-1 specifically promotes the transcription of matrix metalloproteinases, contributing to invasive progression [54]. Such invasive behavior has also been linked to turnover of Focal Adhesions by AIB1 through an AP-1 dependent interaction [55]. Of note, the AIB1Δ4 isoform contains the domains necessary to interact with AP-1 and FAK, which may explain some of its endogenous role, as well as a dual functionality of this oncogenic isoform [25, 55].

Many recent publications have implicated YAP and TAZ, effectors negatively regulated by Hippo Signaling pathway, as potent oncogenes critical to the

*Oncogenic effects and gene expression changes involving direct AIB1 interaction with transcription factors and membrane proteins. Graphical depiction of AIB1 interaction with binding partners, resulting phenotypic*  the cytosol to increase nuclear translocation. Thus, many growth factors signaling cascades converge on transcription factors and AIB1. We have selected a few of the most well studied oncogenic transcription factors whose activity is increased by AIB1 in cancer. **Figure 2** illustrates these interactions and their phenotypic consequences.
