Abstract
Increased cell migration and invasion lead to cancer metastasis and are crucial to cancer prognosis. In this study, we explore whether FBXW7 plays any role in metastatic process. We show that depletion of FBXW7 induces epithelial-mesenchymal transition (EMT) in human colon cancer cells along with the increase in cell migration and invasion. Moreover, FBXW7 deficiency promotes the generation of colon cancer stem-like cells in tumor-sphere culture. mTOR inhibition by rapamycin suppresses FBXW7 loss-driven EMT, invasion and stemness. Our results define the FBXW7/mTOR axis as a novel EMT pathway that mediates cancer invasion.
Published by Elsevier Inc.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Blotting, Western
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Movement
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Cell Shape
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Colorectal Neoplasms / metabolism
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Colorectal Neoplasms / pathology*
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Epithelial-Mesenchymal Transition*
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F-Box Proteins / genetics
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F-Box Proteins / metabolism*
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F-Box-WD Repeat-Containing Protein 7
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Gene Expression Regulation, Neoplastic*
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HCT116 Cells
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Humans
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Neoplasm Invasiveness / pathology
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Neoplastic Stem Cells / metabolism
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Neoplastic Stem Cells / pathology
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Sirolimus / pharmacology*
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TOR Serine-Threonine Kinases / antagonists & inhibitors
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism*
Substances
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Cell Cycle Proteins
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F-Box Proteins
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F-Box-WD Repeat-Containing Protein 7
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FBXW7 protein, human
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Ubiquitin-Protein Ligases
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MTOR protein, human
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TOR Serine-Threonine Kinases
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Sirolimus