Role of the DEK oncogene in the development of squamous cell carcinoma
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REVIEW ARTICLE
Role of the DEK oncogene in the development of squamous cell carcinoma Kazuhisa Ishida1,2 · Takayuki Nakashima1,2 · Toshiyuki Shibata2 · Akira Hara1 · Hiroyuki Tomita1 Received: 1 April 2020 / Accepted: 21 June 2020 © The Author(s) 2020
Abstract DEK is a highly conserved nuclear factor that plays an important role in the regulation of multiple cellular processes. DEK was discovered to be an oncogene as a fusion with NUP214 gene, which results in producing DEK-NUP214 proteins, in a subset of patients with acute myeloid leukemia. Subsequently, DEK overexpression was reported in many cancers, thus DEK itself is considered to be an oncoprotein. DEK has been reported to play important roles in the progression of early and late stage squamous cell carcinoma (SCC) and is useful for early diagnosis of the disease. These findings have made DEK an attractive therapeutic target, especially for human papillomavirus (HPV)-associated SCC. However, the mechanism of DEK in SCC remains unclear. In this review, we discuss human DEK oncogene-related SCC. Keywords DEK · Oncogene · Squamous cell carcinoma
Introduction The DEK oncogene was initially identified as a target of recurrent t(6;9) translocation, resulting in a fusion with the nuclear pore complex protein-encoding gene NUP214 in a subset of patients with acute myeloid leukemia (AML) [1, 2]. DEK is a highly conserved nuclear factor and the only member of its protein class, and it has been shown to be preferentially expressed in aggressively proliferating malignant cells. The DEK gene is located on chromosome 6p22 − 23 and encodes a 375-amino acid (43 kDa) protein that is abundant in the nucleus where it plays key roles in the architectural control of chromatin assembly [3, 4]. DEK also plays a pivotal role in multiple cellular activities and various cellular metabolic processes, such as maintenance of heterochromatin integrity, transcriptional regulation, mRNA splicing, DNA replication, and DNA repair damage and susceptibility [5]. DEK is a Su(var) gene that functions as a positive regulator of heterochromatin, acting through heterochromatin * Hiroyuki Tomita h_tomita@gifu‑u.ac.jp 1
Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1‑1 Yanagido, Gifu 501‑1194, Japan
Department of Oral Maxillofacial Surgery, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan
2
protein 1α (HP1α), which is necessary for the maintenance of heterochromatin integrity [6]. Through its roles in regulating chromatin topology, DEK also regulates various signaling pathways and transcription factors associated with stem cell proliferation, differentiation, and self-renewal [6]. Some reports in humans and Drosophila have demonstrated that DEK inhibits the histone acetyltransferases p300 and p300/ CBP-associating factor (PCAF), resulting in histone H3 and H4 hypoacetylation [7, 8]. However, it is unclear whether DEK is essential for heterochromatin establishment and maintaining the balance between heterochromatin, euchromatin, and chromat
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