Original Articles: Basic scienceTacrolimus and ascomycin inhibit melanoma cell growth, migration and invasion via targeting nuclear factor of activated T-cell 3Xiao, Tiana; Chen, Wenconga; Wang, Shuangfenga; Huang, Shiyinga; Chiang, Chengyaoa; Zou, Yongdongb; Zhao, Yongxiangc; Zheng, DuoaAuthor Information aGuangdong Key Laboratory for Genome Stability and Disease Prevention, Shenzhen Key Laboratory of Translational Medicine of Tumor, Carson International Cancer Center and Department of Cell Biology and Genetics, Shenzhen University School of Medicine bShenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong cNational Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi, China Received 17 April 2019 Accepted 27 February 2020 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.melanomaresearch.com. Correspondence to Duo Zheng, PhD, Department of Cell Biology and Genetics, Shenzhen University Health Sciences Center, 3688 Nanhai Ave, Shenzhen, Guangdong 518060, China, Tel: +86 755 86674681; fax: +86 755 86671906; e-mail: firstname.lastname@example.org Melanoma Research: August 2020 - Volume 30 - Issue 4 - p 325-335 doi: 10.1097/CMR.0000000000000663 Buy SDC Metrics Abstract Melanoma is the most malignant form of skin cancer with high metastatic potential. Nuclear factor of activated T-cells (NFATs) are discovered as transcription factors that regulate the expression of proinflammatory cytokines and other genes during the immune response. Among five NFAT members, NFAT3 is exclusively not expressed in immune cells and its role in progression of different types of cancer remains controversial. Our previous study showed that NFAT3 was highly expressed in skin cancer compared with normal skin tissues and critical for melanoma cell survival and tumor growth. Here, we reported that knockdown of NFAT3 expression, as well as treatment with the calcineurin (CaN) inhibitors, tacrolimus (FK506) or ascomycin (FK520) inhibits melanoma cell migration and invasion, and also proliferation and colony formation. Mechanistic studies revealed that FK506 or FK520 blocked the nuclear translocation and reduced the transcriptional activity of NFAT3. These data support that the antimelanoma effect of FK506 and FK520 is partially mediated by inhibiting the oncogenic factor NFAT3, suggesting that therapeutics based on NFAT3 inhibition may be effective in clinical melanoma treatment. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.