Research ArticleCancer

The transcription factor FOXF1 promotes prostate cancer by stimulating the mitogen-activated protein kinase ERK5

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Science Signaling  10 May 2016:
Vol. 9, Issue 427, pp. ra48
DOI: 10.1126/scisignal.aad5582

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Out-FOXing prostate cancer

Some types of prostate cancer can be aggressive, and these metastatic forms of the disease have few treatment options. Fulford et al. found that prostate tumors from some patients express the gene encoding the transcription factor forkhead box F1 (FOXF1), which is not expressed in normal prostate epithelium. Overexpressing FOXF1 increased tumor growth and metastatic progression when tumor cells were implanted into mice. FOXF1 bound to and increased the expression of genes encoding the kinase ERK5 and two upstream kinases, MAP3K2 and WNK1. Pharmacologically inhibiting ERK5 or knocking down FOXF1, ERK5, or both MAP3K2 and WNK1 suppressed prostate tumor growth and metastasis. The findings indicate targets for personalizing therapeutic intervention in prostate cancer patients with FOXF1-positive tumors.

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