The TGF-β signalling negative regulator PICK1 represses prostate cancer metastasis to bone
The TGF-β signalling negative regulator PICK1 represses prostate cancer metastasis to bone
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TGF-β 信号负调节器 PICK1 抑制前列腺癌骨转移
DOI：
10.1038/bjc.2017.212
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发表时间：
2017-08-22
影响因子：
8.8
通讯作者：
Peng, Xinsheng
中科院分区：
文献类型：
--
作者：
Dai, Yuhu;Ren, Dong;Peng, Xinsheng
背景：TGF-β信号的组成性激活是前列腺癌骨转移的公认机制。与PRKCA 1相互作用的蛋白质（PICK 1）是TGF-β途径的关键负调节因子。方法：采用免疫组化（IHC）方法检测198例PCa患者PICK 1的表达，并与骨转移相关性分析。统计分析PICK 1表达与PCa临床病理特征的相关性。结果：PICK 1在有骨转移的PCa组织和骨源性细胞中表达下调，且PICK 1表达下调与血清PSA水平、Gleason分级和骨转移状态呈正相关。PICK 1过表达抑制PCa细胞体外侵袭和迁移以及体内骨转移。我们的研究结果进一步表明，PICK 1的下调是由miR-210- 3 p在骨转移的PCa组织中的过表达引起的。PICK 1与miR-210- 3 p的临床负相关性在PCa tissues.Conclusions中得到证实：我们的研究结果揭示了一种新的功能和临床相关的表观遗传调节机制，用于组成性激活TGF-β信号传导在PCa骨转移中的作用。
Backgroud: Constitutive activation of TGF-beta signalling is a well-recognised mechanism in bone metastasis of prostate cancer (PCa). Protein Interacting with PRKCA 1 (PICK1) is a critical negative regulator of the TGF-beta pathway. However, the clinical significance and biological role of PICK1 in PCa bone metastasis remain obscure.Methods: PICK1 expression is evaluated by immunohistochemistry (IHC) in 198 PCa patients. Statistical analysis is performed to explore correlation between PICK1 expression and clinicopathological features in PCa patients. The biological role of PICK1 is examined in PC-3 and C4-2B cells in vitro and a mouse intracardial model in vivo.Results: PICK1 expression is decreased in PCa tissues with bone metastasis and bone-derived cells and downregulation of PICK1 positively correlates with serum PSA level, Gleason grade and bone metastasis status in PCa patients. Overexpression of PICK1 suppresses PCa cell invasion and migration in vitro and bone metastasis in vivo. Our results further indicate downregulation of PICK1 is caused by miR-210-3p overexpression in PCa tissues with bone metastasis. Clinical negative correlation of PICK1 with miR-210-3p is confirmed in PCa tissues.Conclusions: Our findings uncover a novel functionally and clinically relevant epigenetic regulatory mechanism for constitutive activation of TGF-beta signalling in bone metastasis of PCa.