Research ArticleCancer therapy

Loss of SPDEF and gain of TGFBI activity after androgen deprivation therapy promote EMT and bone metastasis of prostate cancer

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Sci. Signal.  15 Aug 2017:
Vol. 10, Issue 492, eaam6826
DOI: 10.1126/scisignal.aam6826

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Metastatic effects of primary prostate cancer therapy

Metastatic progression in patients with prostate cancer is common despite pharmacological inhibition of androgen receptor signaling. This drug resistance is associated with increased signaling through the transforming growth factor–β (TGFβ) signaling pathway, and Chen et al. have identified why. In both cultured prostate tumor cells and in tumor-bearing mouse models, the authors found that activation of the androgen receptor induces a transcriptional repressor (called SPDEF) of TGFβ-induced protein (TGFBI), which mediates cell adhesion to the extracellular matrix, a behavior that can facilitate metastasis. However, androgen deprivation therapy (ADT), a common clinical strategy, decreases the abundance of SPDEF and consequently increases that of TGFBI, thereby promoting the metastasis of prostate tumor cells. These findings are another example of how therapies that prevent growth in the primary tumor can inadvertently promote metastasis.