Fucosyltransferase 1 and 2 play pivotal roles in breast cancer cells
| Autor: | Jen-Chine Wu, Hui-Ling Yeo, Ruey-Jen Lin, Tai-Yu Lai, Nai-Chuan Chang, Guo-Shiou Liao, Ching-Liang Ho, I-Ju Chen, Alice L. Yu, Andy C Lee |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Oncology and Carcinogenesis Immunology lcsh:RC254-282 Article Metastasis Extracellular matrix 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Stem Cell Research - Nonembryonic - Human Cancer stem cell Laminin Breast Cancer medicine lcsh:QH573-671 Cell adhesion Cancer biology lcsh:Cytology Cell growth Chemistry Cell migration Cell Biology Stem Cell Research lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Fibronectin 030104 developmental biology 030220 oncology & carcinogenesis Cancer research biology.protein Biochemistry and Cell Biology |
| Zdroj: | Cell Death Discovery, Vol 5, Iss 1, Pp 1-12 (2019) Cell death discovery, vol 5, iss 1 Cell Death Discovery |
| ISSN: | 2058-7716 |
| DOI: | 10.1038/s41420-019-0145-y |
| Popis: | FUT1 and FUT2 encode alpha 1, 2-fucosyltransferases which catalyze the addition of alpha 1, 2-linked fucose to glycans. Glycan products of FUT1 and FUT2, such as Globo H and Lewis Y, are highly expressed on malignant tissues, including breast cancer. Herein, we investigated the roles of FUT1 and FUT2 in breast cancer. Silencing of FUT1 or FUT2 by shRNAs inhibited cell proliferation in vitro and tumorigenicity in mice. This was associated with diminished properties of cancer stem cell (CSC), including mammosphere formation and CSC marker both in vitro and in xenografts. Silencing of FUT2, but not FUT1, significantly changed the cuboidal morphology to dense clusters of small and round cells with reduced adhesion to polystyrene and extracellular matrix, including laminin, fibronectin and collagen. Silencing of FUT1 or FUT2 suppressed cell migration in wound healing assay, whereas FUT1 and FUT2 overexpression increased cell migration and invasion in vitro and metastasis of breast cancer in vivo. A decrease in mesenchymal like markers such as fibronectin, vimentin, and twist, along with increased epithelial like marker, E-cadherin, was observed upon FUT1/2 knockdown, while the opposite was noted by overexpression of FUT1 or FUT2. As expected, FUT1 or FUT2 knockdown reduced Globo H, whereas FUT1 or FUT2 overexpression showed contrary effects. Exogenous addition of Globo H-ceramide reversed the suppression of cell migration by FUT1 knockdown but not the inhibition of cell adhesion by FUT2 silencing, suggesting that at least part of the effects of FUT1/2 knockdown were mediated by Globo H. Our results imply that FUT1 and FUT2 play important roles in regulating growth, adhesion, migration and CSC properties of breast cancer, and may serve as therapeutic targets for breast cancer. |
| Databáze: | OpenAIRE |
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