Estrogen promotes prostate cancer cell migration via paracrine release of ENO1 from stromal cells.
Estrogen promotes prostate cancer cell migration via paracrine release of ENO1 from stromal cells.
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DOI：
10.1210/me.2012-1006
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发表时间：
2012-06
影响因子：
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通讯作者：
Lin Yu;Jiandang Shi;S. Cheng;Yan Zhu;Xiu-min Zhao;Kuo Yang;Xiaoling Du;H. Klocker;Xiaoli Yang-Xia
中科院分区：
文献类型：
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作者：
Lin Yu;Jiandang Shi;S. Cheng;Yan Zhu;Xiu-min Zhao;Kuo Yang;Xiaoling Du;H. Klocker;Xiaoli Yang-Xia
烯醇化酶1（enolase 1，ENO 1）是糖酵解的关键酶，在细胞能量代谢中起重要作用。最近的研究揭示了它在肺癌、头颈癌和乳腺癌的生长和转移中的重要作用。然而，ENO 1表达和分泌的调控机制仍不清楚。我们观察到雌二醇刺激的前列腺基质细胞的条件培养基显著促进前列腺癌（PCa）细胞的迁移。双向蛋白电泳、质谱和免疫耗竭试验确定了条件培养基中的主要活性因子之一为α-烯醇化酶（α-烯醇化酶，或ENO 1）。在前列腺基质细胞中，雌二醇不仅以雌激素受体-α依赖的方式增强了ENO 1蛋白水平的稳定性，而且促进了其分泌到细胞外基质中。此外，重组ENO 1结合到PCa细胞表面，并通过其纤溶酶原受体活性以旁分泌方式促进细胞迁移。免疫组化结果显示，前列腺癌组织间质中的ENO 1水平较正常组织明显升高。
As a key glycolytic enzyme, enolase 1 (ENO1) is critical for cellular energy metabolism. Recent studies have revealed its important role in growth and metastasis of lung, head and neck, and breast cancer. However, the regulatory mechanisms of ENO1 expression and secretion remain unclear. We observed that conditioned medium from estradiol-stimulated prostate stromal cells significantly promoted the migration of prostate cancer (PCa) cells. Two-dimensional protein electrophoresis, mass spectrometry, and immunodepletion assays identified one of the major active factors in the conditioned medium as α-type enolase (α-enolase, or ENO1). Moreover, in prostate stromal cells, estradiol not only enhanced the stability of ENO1 at the protein level in an estrogen receptor-α-dependent manner but also promoted its secretion to the extracellular matrix. Furthermore, recombinant ENO1 bound to the surface of PCa cells and promoted cell migration via their plasminogen receptor activity in a paracrine manner. Immunohistochemistry suggested that stromal ENO1 levels increased in PCa compared with those in normal tissue.