瑞士的一个研究小组8月27日称，他们发现了一种可以阻止人类结肠癌细胞生长和转移的新方法，并在动物实验中获得了成功。相关研究发表在当日出版的《欧洲分子生物学学会期刊》（EMBO Molecular Medicine）上。
据介绍，早期结肠癌的发病部位大多位于肠壁，相对容易治疗。但在日常病例中大多数结肠癌在发现时已到了难以医治的晚期。一家设在瑞士日内瓦的研究小组发现，在结肠癌发展为晚期的过程中，刺猬蛋白信号通路（HH-GLI或Hedgehog-GLI）发挥了重要作用。HH-GLI是一种细胞之间用于传递信息的信号通路，一般被用来确定细胞存活、发育以及位置等信息。
负责此项研究的瑞士日内瓦大学阿瑞尔·鲁伊斯·阿尔塔巴教授说，先前已有相关研究提出，HH-GLI在结肠癌中具有重要作用的假设，但遭到了不少学者的否认。此次，研究人员通过实验证明了HH-GLI在结肠癌生存和发育中的重要作用，并在结肠癌上皮细胞中发现了具有活性的刺猬蛋白。此外，他们还发现转移性肿瘤也必须依靠HH-GLI才能维持生长。因此，识别出HH-GLI并将其作为标靶，就为结肠癌的治疗提供了一种新途径。
具体来说就是运用RNA介入和环耙明阻断癌变组织中Hedgehog信号传导通路，以影响其后续基因表达，从而达到阻止癌细胞生长、转移和复发的目的。
研究人员发现，通过遗传学或者药理学的手段阻断HH-GLI的方法还可以防止癌细胞的自我更新，这种疗法对癌症转移和复发的控制也同样有效。在对小鼠的实验中经过环耙明阻断治疗后，小鼠体内原先存在的肿瘤逐渐消失。患癌小鼠在接受治疗一年之后仍然健康，未见复发或其他不适症状。
鲁伊斯·阿尔塔巴称，这项研究证明了HH-GLI在人类结肠癌细胞中的重要作用，为癌症的治疗开创了一个新局面，提供了一种既能消除肿瘤又能防止其复发和产生副作用的新方法。（生物谷Bioon.com）
生物谷推荐原始出处：
EMBO Molecular Medicine 27 Aug 2009
Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion
Frédéric Varnat 1, Arnaud Duquet 1, Monica Malerba 1, Marie Zbinden 1, Christophe Mas 1, Pascal Gervaz 2, Ariel Ruiz i Altaba 1 *
1Department Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland
2Department of Surgery, University of Geneva Medical School, Geneva University Hospital, Geneva, Switzerland
Human colon cancers often start as benign adenomas through loss of APC, leading to enhanced CATENIN (CAT)/TCF function. These early lesions are efficiently managed but often progress to invasive carcinomas and incurable metastases through additional changes, the nature of which is unclear. We find that epithelial cells of human colon carcinomas (CCs) and their stem cells of all stages harbour an active HH-GLI pathway. Unexpectedly, they acquire a high HEDGEHOG-GLI (HH-GLI) signature coincident with the development of metastases. We show that the growth of CC xenografts, their recurrence and metastases require HH-GLI function, which induces a robust epithelial-to-mesenchymal transition (EMT). Moreover, using a novel tumour cell competition assay we show that the self-renewal of CC stem cells in vivo relies on HH-GLI activity. Our results indicate a key and essential role of the HH-GLI1 pathway in promoting CC growth, stem cell self-renewal and metastatic behavior in advanced cancers. Targeting HH-GLI1, directly or indirectly, is thus predicted to decrease tumour bulk and eradicate CC stem cells and metastases.
