Cripto-1 as a Key Factor in Tumor Progression,Epithelial to Mesenchymal Transition and Cancer Stem Cells |
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Authors: | Hilal Arnouk Gloria Yum Dean Shah |
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Affiliation: | 1.Department of Pathology, College of Graduate Studies, Midwestern University, Downers Grove, IL 60515, USA;2.Chicago College of Optometry, Midwestern University, Downers Grove, IL 60515, USA;3.Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA;4.College of Dental Medicine-Illinois, Midwestern University, Downers Grove, IL 60515, USA;5.Master of Public Health Program, College of Graduate Studies, Midwestern University, Downers Grove, IL 60515, USA |
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Abstract: | Cripto-1 is an essential protein for human development that plays a key role in the early phase of gastrulation in the differentiation of an embryo as well as assists with wound healing processes. Importantly, Cripto-1 induces epithelial to mesenchymal transition to turn fixed epithelial cells into a more mobile mesenchymal phenotype through the downregulation of epithelial adhesion molecules such as E-cadherin, occludins, and claudins, and the upregulation of mesenchymal, mobile proteins, such as N-cadherin, Snail, and Slug. Consequently, Cripto-1’s role in inducing EMT to promote cell motility is beneficial in embryogenesis, but detrimental in the formation, progression and metastasis of malignant tumors. Indeed, Cripto-1 is found to be upregulated in most cancers, such as breast, lung, gastrointestinal, hepatic, renal, cervical, ovarian, prostate, and skin cancers. Through its role in EMT, Cripto-1 can remodel cancer cells to enable them to travel through the extracellular matrix as well as blood and lymphatic vessels to metastasize to different organs. Additionally, Cripto-1 promotes the survival of cancer stem cells, which can lead to relapse in cancer patients. |
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Keywords: | Cripto-1 tumor progression EMT epithelial to mesenchymal transition cancer stem cells biomarker therapeutic target breast cancer melanoma metastasis |
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