Fra-2/AP-1 regulates melanoma cell metastasis by downregulating Fam212b

Chen GL, Li R, Chen XX, Wang J, Cao S, Song R, Zhao MC, Li LM, Hannemann N, Schett G, Qian C, Bozec A (2020)

Publication Type: Journal article

Publication year: 2020


DOI: 10.1038/s41418-020-00660-4


Metastatic melanoma remains a challenging disease. Understanding the molecular mechanisms how melanoma becomes metastatic is therefore of interest. Herein we show that downregulation of the AP-1 transcription factor member Fra-2 in melanoma cells is associated with an aggressive melanoma phenotype in vitro and in vivo. In vitro, Fra-2 knockdown in melanoma cells promoted cell migration and invasion associated with increased Snail-1, Twist-1/2, and matrix metalloproteinase-2 (MMP-2) expression. In vivo, Fra-2 knockdown in a melanoma cell line led to increased metastasis into the lungs and liver. The increased metastatic potential of Fra-2 knockdown melanoma cells was likely due to an accelerated cell cycle transition and increased tissue angiogenesis. Using Fra-2 knockdown cell lines microarray analysis, we identified the protein Fam212b (family with sequence similarity 212 member B) as a downstream target of Fra-2. By additional knockdown of Fam212b in Fra-2 mutant cells, we mitigated the cell migration, invasion, and cell cycle transition phenotype induced by Fra-2 knockdown. Furthermore, Fam212b overexpression enhanced β-catenin pathway. Finally, Fam212b expression is correlated with increased melanoma metastasis and poor clinical outcomes in human patients. In summary, these findings reveal the Fra-2-Fam212b axis as a new pathway of melanoma metastasis, which can be in the future used as potential marker of the metastatic properties of melanoma.

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Chen, G.L., Li, R., Chen, X.X., Wang, J., Cao, S., Song, R.,... Bozec, A. (2020). Fra-2/AP-1 regulates melanoma cell metastasis by downregulating Fam212b. Cell Death and Differentiation.


Chen, Guang Liang, et al. "Fra-2/AP-1 regulates melanoma cell metastasis by downregulating Fam212b." Cell Death and Differentiation (2020).

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