NFAT5 promotes in vivo development of murine melanoma metastasis
- Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South (Korea, Republic of)
Highlights: • First time to demonstrate a role of NFAT5 in the development of melanoma. • Depletion of NFAT5 suppresses cell proliferation and migration in vitro. • Depletion of NFAT5 suppresses tumor growth and metastasis in vivo. • NFAT5 as a novel therapeutic target in melanoma. 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.
- OSTI ID:
- 23107764
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 505, Issue 3; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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