瑞士的一個(gè)研究小組8月27日稱，他們發(fā)現(xiàn)了一種可以阻止人類結(jié)腸癌細(xì)胞生長(zhǎng)和轉(zhuǎn)移的新方法,，并在動(dòng)物實(shí)驗(yàn)中獲得了成功,。相關(guān)研究發(fā)表在當(dāng)日出版的《歐洲分子生物學(xué)學(xué)會(huì)期刊》（EMBO Molecular Medicine）上,。
據(jù)介紹，早期結(jié)腸癌的發(fā)病部位大多位于腸壁,，相對(duì)容易治療,。但在日常病例中大多數(shù)結(jié)腸癌在發(fā)現(xiàn)時(shí)已到了難以醫(yī)治的晚期。一家設(shè)在瑞士日內(nèi)瓦的研究小組發(fā)現(xiàn),，在結(jié)腸癌發(fā)展為晚期的過(guò)程中,，刺猬蛋白信號(hào)通路（HH-GLI或Hedgehog-GLI）發(fā)揮了重要作用。HH-GLI是一種細(xì)胞之間用于傳遞信息的信號(hào)通路,，一般被用來(lái)確定細(xì)胞存活,、發(fā)育以及位置等信息。
負(fù)責(zé)此項(xiàng)研究的瑞士日內(nèi)瓦大學(xué)阿瑞爾·魯伊斯·阿爾塔巴教授說(shuō),，先前已有相關(guān)研究提出,，HH-GLI在結(jié)腸癌中具有重要作用的假設(shè)，但遭到了不少學(xué)者的否認(rèn),。此次,，研究人員通過(guò)實(shí)驗(yàn)證明了HH-GLI在結(jié)腸癌生存和發(fā)育中的重要作用，并在結(jié)腸癌上皮細(xì)胞中發(fā)現(xiàn)了具有活性的刺猬蛋白,。此外,，他們還發(fā)現(xiàn)轉(zhuǎn)移性腫瘤也必須依靠HH-GLI才能維持生長(zhǎng)。因此,，識(shí)別出HH-GLI并將其作為標(biāo)靶,，就為結(jié)腸癌的治療提供了一種新途徑。
具體來(lái)說(shuō)就是運(yùn)用RNA介入和環(huán)耙明阻斷癌變組織中Hedgehog信號(hào)傳導(dǎo)通路,，以影響其后續(xù)基因表達(dá)，從而達(dá)到阻止癌細(xì)胞生長(zhǎng),、轉(zhuǎn)移和復(fù)發(fā)的目的,。
研究人員發(fā)現(xiàn)，通過(guò)遺傳學(xué)或者藥理學(xué)的手段阻斷HH-GLI的方法還可以防止癌細(xì)胞的自我更新,，這種療法對(duì)癌癥轉(zhuǎn)移和復(fù)發(fā)的控制也同樣有效,。在對(duì)小鼠的實(shí)驗(yàn)中經(jīng)過(guò)環(huán)耙明阻斷治療后，小鼠體內(nèi)原先存在的腫瘤逐漸消失,?；及┬∈笤诮邮苤委熞荒曛笕匀?a href="http://hnhlg.com/news/list-54.html" target="_blank">健康，未見(jiàn)復(fù)發(fā)或其他不適癥狀,。
魯伊斯·阿爾塔巴稱,，這項(xiàng)研究證明了HH-GLI在人類結(jié)腸癌細(xì)胞中的重要作用，為癌癥的治療開(kāi)創(chuàng)了一個(gè)新局面,，提供了一種既能消除腫瘤又能防止其復(fù)發(fā)和產(chǎn)生副作用的新方法,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
