Research ArticleCancer

Epigenetic Activation of AP1 Promotes Squamous Cell Carcinoma Metastasis

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Science Signaling  30 Apr 2013:
Vol. 6, Issue 273, pp. ra28
DOI: 10.1126/scisignal.2003884

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Targeting Metastasis

Gene expression can be affected not only by mutations in a gene but also by epigenetic changes, such as histone methylation status. Ding et al. found that histone methylation by KDM4A was important in mediating a positive feedback loop in squamous cell carcinoma (SCC) that enabled the transcription factor complex AP1 (activating protein 1) to induce the expression of its component transcription factors, JUN and FOSL1, implicated in metastatic cancer. Depletion of KDM4A suppressed invasion by SCC cells in vitro and decreased the incidence of lymph node metastasis of SCC tumors in a mouse cancer model. The abundance of KDM4A correlated with that of JUN and FOSL1 in human primary SCC and metastatic SCC tissue. The findings suggest that KDM4A could be targeted to prevent metastasis of SCC.

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