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- W1978768249 abstract "The most devastating aspect of cancer is the emergence of metastases. Thus, identification of potentially metastatic cells among a tumor cell population and the underlying molecular changes that switch cells to a metastatic state are among the most important issues in cancer biology. Here we show that, although normal human colonic epithelial cells lack the glycosphingolipid globotriaosylceramide (Gb 3 ), this molecule is highly expressed in metastatic colon cancer. In addition, a subpopulation of cells that are greatly enriched in Gb 3 and have an invasive phenotype was identified in human colon cancer cell lines. In epithelial cells in culture, Gb 3 was necessary and sufficient for cell invasiveness. Transfection of Gb 3 synthase, resulting in Gb 3 expression in noncancerous polarized epithelial cells lacking endogenous Gb 3 , induced cell invasiveness. Furthermore, Gb 3 knockdown by small inhibitory RNA in colon cancer epithelial cells inhibited cell invasiveness. Gb 3 is the plasma membrane receptor for Shiga toxin 1. The noncatalytic B subunit of Shiga toxin 1 causes apoptosis of human colon cancer cells expressing Gb 3 . Injections of the B subunit of Shiga toxin 1 into HT29 human colon cancer cells engrafted into the flanks of nude mice inhibited tumor growth. These data demonstrate the appearance of a subpopulation of Gb 3 containing epithelial cells in the metastatic stage of human colon cancer and suggest their possible role in colon cancer invasiveness." @default.
- W1978768249 created "2016-06-24" @default.
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- W1978768249 date "2005-12-19" @default.
- W1978768249 modified "2023-09-26" @default.
- W1978768249 title "The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer" @default.
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- W1978768249 doi "https://doi.org/10.1073/pnas.0506474102" @default.
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