Phosphorylation of NFAT3 by CDK3 induces cell transformation and promotes tumor growth in skin cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-11-28

AUTHORS

T Xiao, J J Zhu, S Huang, C Peng, S He, J Du, R Hong, X Chen, A M Bode, W Jiang, Z Dong, D Zheng

ABSTRACT

The nuclear factor of activated T cells (NFAT) family proteins are transcription factors that regulate the expression of pro-inflammatory cytokines and other genes during the immune response. Although the NFAT proteins have been extensively investigated in the immune system, their role in cancer progression remains controversial. Here, we report that NFAT3 is highly expressed in various skin cancer cell lines and tumor tissues. Knockdown of endogenous NFAT3 expression by short hairpin RNA (shRNA) significantly inhibited tumor cell proliferation, colony formation and anchorage-independent cell growth. Furthermore, results of the mammalian two-hybrid assay showed that cyclin-dependent kinase 3 (CDK3) directly interacted with NFAT3 and phosphorylated NFAT3 at serine 259 (Ser259), which enhanced the transactivation and transcriptional activity of NFAT3. The phosphorylation site of NFAT3 was critical for epidermal growth factor (EGF)-stimulated cell transformation of the HaCaT immortalized skin cell line and mutation of NFAT3 at Ser259 led to a reduction of colony formation in soft agar. We also found that overexpressing wildtype NFAT3, but not mutant NFAT3-S259A, promoted A431 xenograft tumor growth. Importantly, we showed that CDK3, NFAT3 and phosphorylated NFAT3-Ser259 were highly expressed in skin cancer compared with normal skin tissues. These results provided evidence supporting the oncogenic potential of NFAT3 and suggested that CDK3-mediated phosphorylation of NFAT3 has an important role in skin tumorigenesis. More... »

PAGES

2835-2845

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/onc.2016.434

DOI

http://dx.doi.org/10.1038/onc.2016.434

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27893713


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47 cell proliferation
48 cell transformation
49 colony formation
50 cyclin-dependent kinase 3
51 cytokines
52 epidermal growth factor
53 evidence
54 expression
55 factors
56 family proteins
57 formation
58 genes
59 growth
60 growth factor
61 hairpin RNA
62 immune response
63 immune system
64 important role
65 induces cell transformation
66 kinase 3
67 knockdown
68 lines
69 mutations
70 normal skin tissues
71 nuclear factor
72 oncogenic potential
73 phosphorylation
74 phosphorylation sites
75 potential
76 pro-inflammatory cytokines
77 progression
78 proliferation
79 protein
80 reduction
81 response
82 results
83 role
84 serine 259
85 short hairpin RNA
86 sites
87 skin cancer
88 skin cancer cell lines
89 skin cell lines
90 skin tissue
91 skin tumorigenesis
92 soft agar
93 system
94 tissue
95 transactivation
96 transcription factors
97 transcriptional activity
98 transformation
99 tumor cell proliferation
100 tumor growth
101 tumor tissue
102 tumorigenesis
103 two-hybrid
104 xenograft tumor growth
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