文章：

Hedgehog基因信号在癌症形成和维持中的作用

Hedgehog signalling in cancer formation and maintenance

原文发布日期：2003-12-01

DOI: 10.1038/nrc1229

类型: Review Article

开放获取: 否

要点：

1. Hedgehog (HH) signalling is required for cell differentiation and organ formation during embryogenesis. In the adult, HH signalling remains active in some organs where it has been implicated in the regulation of stem-cell maintenance and proliferation.
2. HH signalling targets include genes that are important for cell proliferation — proto-oncogenes — as well as growth factors.
3. Misregulation of HH signalling has been shown to cause formation of basal-cell carcinoma and medulloblastoma, and mutations of HH pathway components have been found both in familial and sporadic cases. More recently, small-cell lung cancer (SCLC) and pancreatic adenocarcinoma have been linked to HH signalling, providing a molecular mechanism for these aggressive diseases.
4. Importantly, HH signalling seems to be required not only for cancer initiation but also for tumour growth and survival of medulloblastomas, SCLC and pancreatic adenocarcinoma.
5. HH inhibitors could provide novel therapeutic approaches for treatment of otherwise hard to cure cancer types. Synthetic compounds have been identified that act as HH inhibitors in a very specific manner.

要点翻译：

1. 刺猬（HH）信号在胚胎发生过程中对细胞分化和器官形成至关重要。在成体中，HH信号在某些器官中仍保持活性，参与调控干细胞的维持与增殖。
2. HH信号的靶点包括对细胞增殖至关重要的基因——原癌基因——以及生长因子。
3. HH信号的失调已被证明会导致基底细胞癌和髓母细胞瘤的形成，并且在家族性和散发性病例中均发现了HH通路组件的突变。最近，小细胞肺癌和胰腺腺癌也被发现与HH信号有关，这为这些侵袭性疾病的发病机制提供了分子机制解释。
4. 重要的是，HH信号似乎不仅对癌症的发生是必需的，而且对髓母细胞瘤、小细胞肺癌和胰腺腺癌的肿瘤生长和生存也至关重要。
5. HH抑制剂可能为治疗其他难以治愈的癌症类型提供新的治疗途径。目前已发现能以高度特异性方式作为HH抑制剂的合成化合物。

英文摘要：

The Hedgehog signalling pathway is essential for numerous processes during embryonic development. Members of this family of secreted proteins control cell proliferation, differentiation and tissue patterning in a dose-dependent manner. Although the overall activity of the pathway is diminished after embryogenesis, recent reports show that the pathway remains active in some adult tissues, including adult stem cells in the brain and skin. There is also evidence that uncontrolled activation of the pathway results in specific types of cancer.

摘要翻译： 

Hedgehog信号通路在胚胎发育过程中的众多环节中都至关重要。该家族分泌蛋白的成员以剂量依赖的方式调控细胞增殖、分化及组织模式形成。尽管该通路在胚胎生成后的整体活性降低，近期研究仍显示其在某些成体组织（包括大脑和皮肤中的成体干细胞）中保持活跃。亦有证据表明，该通路的失控激活会导致特定类型的癌症。

原文链接：

Hedgehog signalling in cancer formation and maintenance