Regulation of angiogenesis via Notch signaling in breast cancer and cancer stem cells |
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Authors: | Weiqiang Zhou Guangdi Wang Shanchun Guo |
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Affiliation: | 1. Key Laboratory of Environmental Pollution and Microecology of Liaoning Province, Shenyang Medical College, No. 146 North Huanghe St, Huanggu Dis, Shenyang City, Liaoning Pro 110034, PR China;2. Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA;3. Microbiology, Biochemistry & Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA |
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Abstract: | Breast cancer angiogenesis is elicited and regulated by a number of factors including the Notch signaling. Notch receptors and ligands are expressed in breast cancer cells as well as in the stromal compartment and have been implicated in carcinogenesis. Signals exchanged between neighboring cells through the Notch pathway can amplify and consolidate molecular differences, which eventually dictate cell fates. Notch signaling and its crosstalk with many signaling pathways play an important role in breast cancer cell growth, migration, invasion, metastasis and angiogenesis, as well as cancer stem cell (CSC) self-renewal. Therefore, significant attention has been paid in recent years toward the development of clinically useful antagonists of Notch signaling. Better understanding of the structure, function and regulation of Notch intracellular signaling pathways, as well as its complex crosstalk with other oncogenic signals in breast cancer cells will be essential to ensure rational design and application of new combinatory therapeutic strategies. Novel opportunities have emerged from the discovery of Notch crosstalk with inflammatory and angiogenic cytokines and their links to CSCs. Combinatory treatments with drugs designed to prevent Notch oncogenic signal crosstalk may be advantageous over λ secretase inhibitors (GSIs) alone. In this review, we focus on the more recent advancements in our knowledge of aberrant Notch signaling contributing to breast cancer angiogenesis, as well as its crosstalk with other factors contributing to angiogenesis and CSCs. |
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Keywords: | Notch Breast cancer Tumor angiogenesis Oncogenesis Breast cancer stem cells |
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