Romero Diana, Kypta Robert
Department of Surgery and Cancer, Imperial College London, London, UK.
Bioarchitecture. 2013 Mar-Apr;3(2):42-4. doi: 10.4161/bioa.25243. Epub 2013 Mar 1.
The tumor suppressor Dickkopf-3 (Dkk-3) is rather a unique molecule. Although it is related to the Dickkopf family of secreted Wnt antagonists, it does not directly inhibit Wnt signaling, and its function and mechanism of action are unknown. Endogenous Dkk-3 was recently found to be required to limit cell proliferation both in the developing mouse prostate and in 3D cultures of human prostate epithelial cells. Dkk-3 was further shown to modulate the response of normal prostate epithelial cells to transforming growth factor-β (TGF-β). These studies are consistent with a model in which Dkk-3 is required by normal cells to prevent the TGF-β switch from tumor suppressor to tumor promoter. Here, we discuss these findings and their potential impact on the development and progression of prostate cancer.
肿瘤抑制因子Dickkopf-3（Dkk-3）是一种相当独特的分子。尽管它与分泌型Wnt拮抗剂Dickkopf家族相关，但它并不直接抑制Wnt信号传导，其功能和作用机制尚不清楚。最近发现，内源性Dkk-3在发育中的小鼠前列腺以及人前列腺上皮细胞的三维培养中都是限制细胞增殖所必需的。进一步研究表明，Dkk-3可调节正常前列腺上皮细胞对转化生长因子-β（TGF-β）的反应。这些研究与一种模型相符，即正常细胞需要Dkk-3来防止TGF-β从肿瘤抑制因子转变为肿瘤促进因子。在此，我们讨论这些发现及其对前列腺癌发生和发展的潜在影响。
