Crucial role of the transcription factors family activator protein 2 in cancer: current clue and views

Abstract

The transcription factor family activator protein 2 (TFAP2) is vital for regulating both embryonic and oncogenic development. The TFAP2 family consists of five DNA-binding proteins, including TFAP2A, TFAP2B, TFAP2C, TFAP2D and TFAP2E. The importance of TFAP2 in tumor biology is becoming more widely recognized. While TFAP2D is not well studied, here, we mainly focus on the other four TFAP2 members. As a transcription factor, TFAP2 regulates the downstream targets directly by binding to their regulatory region. In addition, the regulation of downstream targets by epigenetic modification, posttranslational regulation, and interaction with noncoding RNA have also been identified. According to the pathways in which the downstream targets are involved in, the regulatory effects of TFAP2 on tumorigenesis are generally summarized as follows: stemness and EMT, interaction between TFAP2 and tumor microenvironment, cell cycle and DNA damage repair, ER- and ERBB2-related signaling pathway, ferroptosis and therapeutic response. Moreover, the factors that affect TFAP2 expression in oncogenesis are also summarized. Here, we review and discuss the most recent studies on TFAP2 and its effects on carcinogenesis and regulatory mechanisms.

Transcription factor activating enhancer-binding protein 2ε (AP2ε) modulates phenotypic plasticity and progression of malignant melanoma

“…This is supported by our data revealing an induction of AP2α expression in the murine melanoma tissue after loss of AP2ε. The interplay of the isoforms, also not understood today, is generally accepted, as summarized in a recent review [ 53 ]. However, studies addressing this aspect are mainly feasible in vivo, like in our study.…”

The Potential of Aqueous Humor Sampling in Diagnosis, Prognosis, and Treatment of Retinoblastoma

“… 37 TFAP2A is a signaling nexus in tumor progression that promotes tumor stemness and triggers epithelial mesenchymal transition (EMT) and metastasis via augmenting the expression of various oncogenes. 38 Plus, epigenetic DNA methylation profiling investigated via targeted bisulfite sequencing uncovered DNA hypermethylation signatures of various promoters in the AH cfDNA including RB1 , AXIN2 , FGFR1 (fibroblast growth factor receptor 1), GSTA4 (glutathione S-transferase alpha 4), IL1R2 (interleukin 1 receptor 2), STK19 (serine/threonine kinase 19), and TFF1 (trefoil factor 1), and DNA hypomethylation of the MYCN and SYK promotors in corroboration with RB tumor methylation signatures. 39 The mechanisms leading to these aberrant methylation patterns remain unknown.…”

Multi-omic characterization of ILC and ILC-like cell lines as part of ILC cell line encyclopedia (ICLE) defines new models to study potential biomarkers and explore therapeutic opportunities

“…TFAPAB gene is an emerging biomarker of lobular disease that is preferentially expressed in both precursor and invasive stages (87,88). Importantly, it controls differentiation and proliferation of tumor cells and has potential to serve as prognostic biomarker or a targetable vulnerability in ILC disease (105,106). Using integrative analysis of DNAm and RNA expression, we revealed epigenetic activation of TFAP2B gene in both ILC/ILC-like breast cancer cell lines and ILC tumors.…”