AEBP1 is a Novel Oncogene: Mechanisms of Action and Signaling Pathways

Abstract

Adipocyte enhancer-binding protein 1 (AEBP1) is a transcriptional repressor involved in the regulation of critical biological processes including adipogenesis, mammary gland development, inflammation, macrophage cholesterol homeostasis, and atherogenesis. Several years ago, we first reported the ability of AEBP1 to exert a positive control over the canonical NF-κB pathway. Indeed, AEBP1 positively regulates NF-κB activity via its direct interaction with IκBα, a key NF-κB inhibitor. AEBP1 overexpression results in uncontrollable activation of NF-κB, which may have severe pathogenic outcomes. Recently, the regulatory relationship between AEBP1 and NF-κB pathway has been of great interest to many researchers primarily due to the implication of NF-κB signaling in critical cellular processes such as inflammation and cancer. Since constitutive activation of NF-κB is widely implicated in carcinogenesis, AEBP1 overexpression is associated with tumor development and progression. Recent studies sought to explore the effects of the overexpression of AEBP1, as a potential oncogene, in different types of cancer. In this review, we analyze the effects of AEBP1 overexpression in a variety of malignancies (e.g., breast cancer, glioblastoma, bladder cancer, gastric cancer, colorectal cancer, ovarian cancer, and skin cancer), with a specific focus on the AEBP1-mediated control over the canonical NF-κB pathway. We also underscore the ability of AEBP1 to regulate crucial cancer-related events like cell proliferation and apoptosis in light of other key pathways (e.g., PI3K-Akt, sonic hedgehog (Shh), p53, parthanatos (PARP-1), and PTEN). Identifying AEBP1 as a potential biomarker for cancer prognosis may lead to a novel therapeutic target for the prevention and/or treatment of various types of cancer.

AEBP1 Promotes Glioblastoma Progression and Activates the Classical NF-κB Pathway

“…Previous studies have focused on the role of AEBP1 in GBM in relationship with apoptosis [ 13 , 14 ] as well as other tumorigenic characteristics [ 5 ]. In this study, we further investigated the roles of AEBP1 in GBM progression via a series of in vitro and in vivo analyses.…”

“…Adipocyte enhancer-binding protein 1 ( AEBP1 ) is a transcriptional repressor with carboxypeptidase (CP) activity. The AEBP1 protein could positively regulate the activity of MAP kinase (MAPK) in adipocytes, thus stimulating adipocyte proliferation and reducing adipocyte differentiation; the proteins can also positively regulate NF- κ B activity in macrophages by promoting I-kappa-B-alpha (NFKBIA) phosphorylation and subsequent degradation, thereby enhancing the inflammatory responsiveness of macrophages [ 5 ]. AEBP1 is involved in the progression of a variety of diseases, such as abdominal aortic aneurysm [ 6 ], nonalcoholic steatohepatitis [ 7 ], Ehlers-Danlos syndrome [ 8 ], and Alzheimer's disease [ 9 ].…”

“…AEBP1 is involved in the progression of a variety of diseases, such as abdominal aortic aneurysm [ 6 ], nonalcoholic steatohepatitis [ 7 ], Ehlers-Danlos syndrome [ 8 ], and Alzheimer's disease [ 9 ]. Studies have shown that AEBP1 is highly expressed in a variety of malignant tumors (such as breast cancer, glioblastoma, bladder cancer, gastric cancer, colorectal cancer, ovarian cancer, and skin cancer) [ 5 ]. AEBP1 can promote proliferation, metastasis, angiogenesis, and inflammation and suppress apoptosis both in vitro and in vivo; therefore, it acts as an oncogene to promote tumor progression [ 5 ].…”

“…Studies have shown that AEBP1 is highly expressed in a variety of malignant tumors (such as breast cancer, glioblastoma, bladder cancer, gastric cancer, colorectal cancer, ovarian cancer, and skin cancer) [ 5 ]. AEBP1 can promote proliferation, metastasis, angiogenesis, and inflammation and suppress apoptosis both in vitro and in vivo; therefore, it acts as an oncogene to promote tumor progression [ 5 ]. For example, upregulation of AEBP1 in colon cancer accelerates the progression of colon cancer by promoting angiogenesis [ 10 ].…”

IGFBP2 is a Potential Master-Regulator Driving Dysregulated Gene Network Responsible for Short Survival in Glioblastoma Multiforme

“…"OSMR is a critical regulator of glioblastoma tumor growth that orchestrates a feed-forward signalling mechanism with EGFRvIII and STAT3 to drive tumorigenesis" 24 .AEBP1 -is a critical oncogene and "both cellular proliferation and survival were affected upon AEBP1 silencing" in glioma cells. AEBP1 overexpression leads to "uncontrollable activation of NF-κB, which may have severe pathogenic outcomes" in GBM 25 Except VEGFA, all master regulators were found to impact survival according to TCGA-GBM RNA seq data. Master regulators were differentially expressed across the survival groups and the expression patterns are validated in 2 other independent cohorts.…”