期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 100, 期 20, 页码 11445-11450出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2034995100
关键词
-
资金
- NCI NIH HHS [T32 CA009594, 5T32CA09594] Funding Source: Medline
- NIGMS NIH HHS [GM61712, R01 GM061712] Funding Source: Medline
CD95 type I and 11 cells differ in their dependence on mitochondria to execute apoptosis, because antiapoptotic members of the Bcl-2 family render only type 11 cells resistant to death receptor-induced apoptosis. They can also be distinguished by a more efficient formation of the death-inducing signaling complex in type I cells. We have identified a soluble form of CD95 ligand (S2) that is cytotoxic to type 11 cells but does not kill type I cells. By testing 58 tumor cell lines of the National Cancer Institute's anticancer drug-screening panel for apoptosis sensitivity to S2 and performing death-inducing signaling complex analyses, we determined that half of the CD95-sensitive cells are type I and half are type II. Most of the type I cell lines fall into a distinct class of tumor cells expressing mesenchymal-like genes, whereas the type 11 cell lines preferentially express epithelium-like markers. This suggests that type I and 11 tumor cells represent different stages of carcinogenesis that resemble the epithelial-mesenchymal transition. We then screened the National Cancer Institute database of >42,000 compounds for reagents with patterns of growth inhibition that correlated with either type I or type 11 cell lines and found that actin-binding compounds selectively inhibited growth of type I cells, whereas tubulin-interacting compounds inhibited growth of type 11 cells. Our analysis reveals fundamental differences in programs of gene expression between type I and type 11 cells and could impact the way actin- and microtubule-disrupting antitumor agents are used in tumor therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据