Hedgehog signalling in prostate regeneration, neoplasia and metastasis
Hedgehog signalling in prostate regeneration, neoplasia and metastasis
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DOI：
10.1038/nature02962
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发表时间：
2004-10-07
期刊：
影响因子：
64.8
通讯作者：
Beachy, PA
中科院分区：
文献类型：
--
作者：
Karhadkar, SS;Bova, GS;Beachy, PA
转移性癌症在发育或再生器官中具有正常细胞的某些特性，例如增殖和改变组织组织的能力。我们在这里发现，在发育模式（1-6）中起重要作用的Hedgehog （Hh）信号通路的活性是前列腺上皮再生所必需的，并且持续的通路激活转化前列腺祖细胞并使其致瘤性。通路活性升高进一步区分转移性前列腺癌和局限性前列腺癌，通路操作可以调节侵袭性和转移。通路活性是由Hh配体的内源性表达触发的，并且依赖于Smoothened的表达，Smoothened是一种必要的Hh应答成分（1,2,7），在良性前列腺上皮细胞中不表达。因此，监测和控制Hh通路活性可能为具有转移潜力的前列腺癌的诊断和治疗提供重大改进。
Metastatic cancers adopt certain properties of normal cells in developing or regenerating organs, such as the ability to proliferate and alter tissue organization. We find here that activity of the Hedgehog (Hh) signalling pathway, which has essential roles in developmental patterning(1-6), is required for regeneration of prostate epithelium, and that continuous pathway activation transforms prostate progenitor cells and renders them tumorigenic. Elevated pathway activity furthermore distinguishes metastatic from localized prostate cancer, and pathway manipulation can modulate invasiveness and metastasis. Pathway activity is triggered in response to endogenous expression of Hh ligands, and is dependent upon the expression of Smoothened, an essential Hh response component(1,2,7) that is not expressed in benign prostate epithelial cells. Monitoring and manipulating Hh pathway activity may thus offer significant improvements in diagnosis and treatment of prostate cancers with metastatic potential.