肿瘤干细胞引发原发性肿瘤的机制

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肿瘤干细胞启动、促使癌细胞生长的理论现已成为临床和基础研究领域的主流观点。最近有研究不仅鉴别出肿瘤干细胞，而且还证实了如果将肿瘤干细胞移植到第二中间宿主后会引发肿瘤。但目前研究者们对当初干细胞是如何突变并引发原发性肿瘤的过程仍不清楚。

Li实验室以小鼠的肠道系统为研究模型，将其中人类肿瘤抑制基因PTEN敲除，发现PTEN/Akt信号通路通过磷酸化β-catenin（包括第552位点的丝氨酸），参与调控β-catenin的细胞核定位，从而调节干细胞的活性。

“我们发现如果肠上皮细胞和基质细胞的PTEN都丢失了，会引起一些改变，如干细胞数量增加，以及它们位置或定位的改变。” Li介绍说，“这些改变会导致腺窝分裂（**）和出芽，有可能导致肠息肉病（***）和肿瘤生长失控。”

“参与此项研究的所有人员都为能揭示肿瘤干细胞的基本特征兴奋不已。” He说道，“从研究中我们知道，肿瘤干细胞只占肿瘤团块的一小部分，它们细胞周期较为缓慢但仍比正常干细胞活跃，肿瘤干细胞以及基质细胞的参与引发了原发性肿瘤。所有这些发现都将影响我们今后的工作。”

英文原文：

PTEN-deficient intestinal stem cells initiate intestinal polyposis

The theory that cancer stem cells initiate and drive cancer cell growth has been gaining popularity in both clinical and basic research. Recent studies have identified cancer stem cells and shown that they may cause tumors when transplanted into a secondary host. Until now, however, little was known about the process by which mutations in a stem cell result in primary tumor initiation.

The Li Lab team studied the intestinal system in mice in which one of the human tumor suppressor genes, PTEN, had been deleted. They found that the PTEN/Akt pathway likely regulates stem cell activation by helping control nuclear localization of beta-catenin, the Wnt pathway effector, through phosphorylation of beta-catenin -- including Serine552.

\"We found that a loss of PTEN in intestinal epithelial cells accompanied by a loss of PTEN in stromal cells can lead to changes that may increase the number of stem cells and change their position or location,\" said Dr. Li. \"These changes result in crypt fission and budding and can lead to intestinal polyposis and uncontrolled tumor growth.\"

\"All of us were very excited to be part of these efforts to reveal basic features of cancer stem cells,\" said Dr. He. \"What we learned -- that cancer stem cells are a rare population in the tumor mass; that they are slow cycling but more active than normal stem cells; and that cancer stem cells and stromal insertions initiate the process of primary tumorigenesis -- will be influential in our future work.\"

\"Findings from the Li Lab create opportunities to further characterize cancer stem cells and to obtain their molecular signature -- providing important insight into targeting these cells,\" said Robb Krumlauf, Ph.D., Scientific Director. \"This is a fascinating new area of cancer research, and Linheng Li and his colleagues will continue to make important contributions.\"