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Biochem Biophys Res Commun. 2019 Jan 29;509(1):82-88. doi: 10.1016/j.bbrc.2018.12.066. Epub 2018 Dec 23.

Overexpression of absent in melanoma 2 in oral squamous cell carcinoma contributes to tumor progression.

Author information

1
Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, University of Miyazaki, Miyazaki, Japan; Division of Oral and Maxillofacial Surgery, Department of Medicine of Sensory and Motor Organs, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
2
Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, University of Miyazaki, Miyazaki, Japan.
3
Division of Oral and Maxillofacial Surgery, Department of Medicine of Sensory and Motor Organs, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
4
Division of Oral and Maxillofacial Surgery, Department of Medicine of Sensory and Motor Organs, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan; Division of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
5
Division of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
6
Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, University of Miyazaki, Miyazaki, Japan. Electronic address: kmorishi@med.miyazaki-u.ac.jp.

Abstract

We had previously reported that in addition to p53 inactivation, overexpression of the DNA sensor protein-absent in melanoma 2 (AIM2)-contributes to tumorigenesis of oral squamous cell carcinoma (OSCC). Given that AIM2 is highly expressed in the OSCC tumors from patients with metastasis, we investigated whether AIM2 expression contributes to the progression of OSCC metastasis. In in vitro assays using OSCC cell lines, the high migration and invasion capacity of OSCC cells were dependent on the increased expression of AIM2, resulting in enhanced epithelial-mesenchymal transition (EMT), with EMT-related gene expression. Moreover, the in vivo short-term metastasis assay using orthotopic implantation into immunodeficient mice demonstrated that OSCC cells with high levels of AIM2 expression exhibited enhanced tumor growth in the tongue, resulting in decreased survival of the mice. Further, the cells overexpressing AIM2 dominantly invaded into the tumor lymphatic vessels, unlike OSCC cells with low AIM2 expression. Thus, the high expression of AIM2 in OSCC enhances progression of tumor growth.

KEYWORDS:

Absent in melanoma 2 (AIM2); Epithelial-mesenchymal transition (EMT); Invasion; Oral squamous cell carcinoma (OSCC)

PMID:
30587341
DOI:
10.1016/j.bbrc.2018.12.066

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