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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1734-1741. Prepublished online as a Blood First Edition Paper on October 19, 2004; DOI 10.1182/blood-2004-05-2042. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-05-2042v1 105/4/1734    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yu, J. L. Articles by Rak, J. W. Search for Related Content PubMed PubMed Citation Articles by Yu, J. L. Articles by Rak, J. W. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis Joanne L. Yu, Linda May, Vladimir Lhotak, Siranoush Shahrzad, Senji Shirasawa, Jeffrey I. Weitz, Brenda L. Coomber, Nigel Mackman, and Janusz W. Rak From the Henderson Research Centre, Experimental Thrombosis Research, McMaster University, Hamilton, ON, Canada; Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada; Department of Pathology, International Medical Center of Japan, Tokyo, Japan; and Departments of Immunology and Vascular Biology, The Scripps Research Institute, La Jolla, CA. Tissue factor (TF) is the primary cellular initiator of blood coagulation and a modulator of angiogenesis and metastasis in cancer. Indeed, systemic hypercoagulability in patients with cancer and TF overexpression by cancer cells are both closely associated with tumor progression, but their causes have been elusive. We now report that in human colorectal cancer cells, TF expression is under control of 2 major transforming events driving disease progression (activation of K-ras oncogene and inactivation of the p53 tumor suppressor), in a manner dependent on MEK/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3'-kinase (PI3K). Furthermore, the levels of cell-associated as well as circulating (microvesicle-associated) TF activity are linked to the genetic status of cancer cells. Finally, RNA interference experiments suggest that TF expression is an important effector of the K-ras-dependent tumorigenic and angiogenic phenotype in vivo. Thus, this study establishes a causal link between cancer coagulopathy, angiogenesis, and genetic tumor progression. (Blood. 2005;105:1734-1741) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Tissue factor and tumor cells: as bad as it gets? Henri H. Versteeg Blood 2005 105: 1374. [Full Text] [PDF] This article has been cited by other articles: R. S. Kasthuri, M. B. Taubman, and N. Mackman Role of Tissue Factor in Cancer J. Clin. Oncol., October 10, 2009; 27(29): 4834 - 4838. [Abstract] [Full Text] [PDF] C. Boccaccio and P. M. Comoglio Genetic Link Between Cancer and Thrombosis J. Clin. Oncol., October 10, 2009; 27(29): 4827 - 4833. [Abstract] [Full Text] [PDF] S. Regina, J.-B. Valentin, S. Lachot, E. Lemarie, J. Rollin, and Y. Gruel Increased Tissue Factor Expression Is Associated with Reduced Survival in Non-Small Cell Lung Cancer and with Mutations of TP53 and PTEN Clin. 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