Tacrolimus and ascomycin inhibit melanoma cell growth, migration and invasion via targeting nuclear factor of activated T-cell 3

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.
Source: Melanoma Research - Category: Cancer & Oncology Tags: Original Articles: Basic science Source Type: research