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Breast cancer phenotypes regulated by tissue factor-factor VII pathway: Possible therapeutic targets

World Journal of Clinical Oncology 2014年第5期5卷 908-920页

作者： shiro koizume Yohei Miyagi Molecular Pathology and Genet-ics Division Kanagawa Cancer Center Research Institute

Breast cancer is a leading cause of cancer death in women, worldwide. Fortunately, breast cancer is relatively chemosensitive, with recent advances leading to the development of effective therapeutic strategies, significantly increasing disease cure rate. However, disease recurrence and treatment of cases lacking therapeutic molecular targets, such as epidermal growth factor receptor 2 and hormone receptors, referred to as triple-negative breast cancers, still pose major hurdles in the treatment of breast cancer. Thus, novel therapeutic approaches to treat aggressive breast cancers are essential. Blood coagulation factor VII(fV II) is produced in the liver and secreted into the blood stream. Tissue factor(TF), the cellular receptor for fV II, is an integral membrane protein that plays key roles in the extrinsic coagulation cascade. TF is overexpressed in breast cancer tissues. The TF-fV II complex may be formed in the absence of injury, because f VII potentially exists in the tissue fluid within cancer tissues. The active form of this complex(TF-fV IIa) may stimulate the expression of numerous malignant phenotypes in breast cancer cells. Thus, the TF-fV II pathway is a potentially attractive target for breast cancer treatment. To date, a number of studies investigating the mecha-nisms by which TF-fV II signaling contributes to breast cancer progression, have been conducted. In this review, we summarize the mechanisms controlling TF and fV II synthesis and regulation in breast cancer cells. Our current understanding of the TF-fV II pathway as a mediator of breast cancer progression will be also described. Finally, we will discuss how this knowledge can be applied to the design of future therapeutic strategies.

关键词： Breast cancer Blood coagulation Tissue factor Coagulation factor VII Gene regulation Therapeutic strategy

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