Nodal promotes the self-renewal of human colon cancer stem cells via an autocrine manner through Smad2/3 signaling pathway.
Nodal promotes the self-renewal of human colon cancer stem cells via an autocrine manner through Smad2/3 signaling pathway.
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DOI：
10.1155/2014/364134
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发表时间：
2014
影响因子：
--
通讯作者：
He Z
中科院分区：
文献类型：
--
作者：
Gong Y;Guo Y;Hai Y;Yang H;Liu Y;Yang S;Zhang Z;Ma M;Liu L;Li Z;He Z
结直肠癌是最常见、最致命的肿瘤之一。然而，结直肠癌发生的分子机制仍未明确。本研究探讨了结肠癌干细胞（CCSCs）中Nodal的表达和功能。结瘤及其受体存在于许多人类结直肠癌细胞系中。NODAL和ALK-4在人结肠癌组织中共表达，而CCSCs标志物NODAL、CD24和CD44在人结肠癌组织中的表达水平高于邻近的非癌性结肠组织。采用抗cd24和抗cd44磁激活细胞分选分离人CCSCs。在CD44或cd24阴性的人结直肠癌细胞系中几乎检测不到Nodal转录物和蛋白，而在CCSCs中存在Nodal及其受体。值得注意的是，Nodal促进了人CCSCs的球形形成，并且在人CCSCs衍生的球形细胞中，Nodal激活了Smad2和Smad3的磷酸化。综上所述，这些结果表明Nodal通过Smad2/3通路以自分泌方式促进人类CCSCs的自我更新，介导人类结直肠癌的癌变。本研究为人类CCSCs命运调控的分子机制提供了新的见解，为人类结直肠癌的基因治疗提供了新的靶点。
Colorectal cancer is one of the most common and fatal tumors. However, molecular mechanisms underlying carcinogenesis of colorectal cancer remain largely undefined. Here, we explored the expression and function of Nodal in colon cancer stem cells (CCSCs). Nodal and its receptors were present in numerous human colorectal cancer cell lines. NODAL and ALK-4 were coexpressed in human colon cancerous tissues, and NODAL, CD24, and CD44, markers for CCSCs, were expressed at higher levels in human colon cancerous tissues than adjacent noncancerous colon tissues. Human CCSCs were isolated by magnetic activated cell sorting using anti-CD24 and anti-CD44. Nodal transcript and protein were hardly detectable in CD44- or CD24-negative human colorectal cancer cell lines, whereas Nodal and its receptors were present in CCSCs. Notably, Nodal facilitated spheroid formation of human CCSCs, and phosphorylation of Smad2 and Smad3 was activated by Nodal in cells of spheres derived from human CCSCs. Collectively, these results suggest that Nodal promotes the self-renewal of human CCSCs and mediate carcinogenesis of human colorectal cancer via an autocrine manner through Smad2/3 pathway. This study provides a novel insight into molecular mechanisms controlling fate of human CCSCs and offers new targets for gene therapy of human colorectal cancer.
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影响因子：
23.9
作者：
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通讯作者：
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影响因子：
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Ibáñez, CF
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作者：
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