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Hedgehog signalling in prostate regeneration, neoplasia and metastasis

机译：刺猬信号在前列腺再生，瘤形成和转移中的作用

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摘要

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.
机译：转移性癌症采用发育或再生器官中正常细胞的某些特性，例如增殖和改变组织结构的能力。我们在这里发现，刺猬（Hh）信号通路的活性在发育模式（1-6）中具有重要作用，是前列腺上皮再生所必需的，并且连续的通路活化会转化前列腺祖细胞并使它们致癌。此外，通路活性的升高将转移性癌与局限性前列腺癌区分开来，通路操纵可调节浸润性和转移性。通路活性是响应Hh配体的内源性表达而触发的，并且依赖于Smoothed的表达，Smoothened是一种在良性前列腺上皮细胞中不表达的重要Hh响应成分（1,2,7）。因此，监测和操纵Hh通路的活性可以显着改善具有转移潜力的前列腺癌的诊断和治疗。

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