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Biochem Biophys Res Commun. 2018 Nov 2;505(3):748-754. doi: 10.1016/j.bbrc.2018.09.171. Epub 2018 Oct 5.

NFAT5 promotes in vivo development of murine melanoma metastasis.

Author information

1
Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea.
2
Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea; College of Medicine, Hanyang University, Seoul, South Korea. Electronic address: ks66kim@hanyang.ac.kr.
3
Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea; College of Medicine, Hanyang University, Seoul, South Korea. Electronic address: suri28@hanyang.ac.kr.

Abstract

Malignant melanoma is one of the most fatal and aggressive skin cancers, originating from pigment-containing melanocytes. Despite progress in clinical research, treatment options for malignant melanoma have been limited. The nuclear factor of activated T-cell 5 (NFAT5), originally identified as tonicity regulated transcription factor Ton/EBP, is now known as a carcinogenic gene in several types of cancer pathology. In this study, we knocked down NFAT5 to investigate its role in melanoma cancer. shRNA-mediated knockdown of NFAT5 led to a significant decrease in cell proliferation in vitro. Additionally, depletion of NFAT5 inhibited the cell migratory ability of B16BL6 melanoma cells and led to more accumulation at the G2/M phase of the cell cycle. Furthermore, NFAT5 was essential for the development of melanoma cancer pathophysiology in an in vivo mouse model. NFAT5 knockdown-induced tumor growth was slow and tumor volume was significantly reduced compared to mock controls. Moreover, NFAT5 knockdown was associated with a low number of metastatic nodules on the lung and liver. To our knowledge, our data demonstrate for the first time a role of NFAT5 in the development of melanoma. We provide evidence for NFAT5 as a marker of cell migration and metastasis, indicating that NFAT5 represents a novel therapeutic target in melanoma.

KEYWORDS:

Cell migration; Cell proliferation; Metastasis; Tumor growth; Tumor nodule

PMID:
30293684
DOI:
10.1016/j.bbrc.2018.09.171
[Indexed for MEDLINE]

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