Inhibition of α(1,6)fucosyltransferase: Effects on Cell Proliferation, Migration, and Adhesion in an SW480/SW620 Syngeneic Colorectal Cancer Model
| Autor: | Rubén López-Cortés, Laura Muinelo-Romay, Almudena Fernández-Briera, Emilio Gil-Martín |
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| Rok vydání: | 2022 |
| Předmět: |
2302.21 Biología Molecular
Organic Chemistry General Medicine Fucosyltransferases FUT8 core fucosylation Lens culinaris agglutinin colorectal cancer proliferation migration cancer progression shRNA Catalysis Computer Science Applications Inorganic Chemistry 2302 Bioquímica Cell Movement Cell Line Tumor Humans Physical and Theoretical Chemistry Colorectal Neoplasms 3207.03 Carcinogénesis Molecular Biology Spectroscopy Cell Proliferation |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 15; Pages: 8463 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms23158463 |
| Popis: | The present study explored the impact of inhibiting α(1,6)fucosylation (core fucosylation) on the functional phenotype of a cellular model of colorectal cancer (CRC) malignization formed by the syngeneic SW480 and SW620 CRC lines. Expression of the FUT8 gene encoding α(1,6)fucosyltransferase was inhibited in tumor line SW480 by a combination of shRNA-based antisense knockdown and Lens culinaris agglutinin (LCA) selection. LCA-resistant clones were subsequently assayed in vitro for proliferation, migration, and adhesion. The α(1,6)FT-inhibited SW480 cells showed enhanced proliferation in adherent conditions, unlike their α(1,6)FT-depleted SW620 counterparts, which displayed reduced proliferation. Under non-adherent conditions, α(1,6)FT-inhibited SW480 cells also showed greater growth capacity than their respective non-targeted control (NTC) cells. However, cell migration decreased in SW480 after FUT8 knockdown, while adhesion to EA.hy926 cells was significantly enhanced. The reported results indicate that the FUT8 knockdown strategy with subsequent selection for LCA-resistant clones was effective in greatly reducing α(1,6)FT expression in SW480 and SW620 CRC lines. In addition, α(1,6)FT impairment affected the proliferation, migration, and adhesion of α(1,6)FT-deficient clones SW480 and SW620 in a tumor stage-dependent manner, suggesting that core fucosylation has a dynamic role in the evolution of CRC. Ministerio de Educación y Ciencia | Ref. AP-FPU12/03662 Xunta de Galicia | Ref. GRC 2014/019 Xunta de Galicia | Ref. CN 2011/024 |
| Databáze: | OpenAIRE |
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