Laminin 521 Modulates the Сytotoxic Effect of 5-Fluorouracil on Colorectal Cancer HT29 Cells
| Autor: | D. V. Maltseva, I.M. Tsypina, V.G. Zgoda, Sergey Nikulin, A. Turchinovich |
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| Rok vydání: | 2019 |
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| Zdroj: | Biotekhnologiya. 35:73-79 |
| ISSN: | 2500-2341 0234-2758 |
| Popis: | The cytotoxic effect of 5-fluorouracil (5FU) and regorafenib (RF)-drugs with different mechanisms of action used to treat colorectal cancer-on the HT29 cell line when cultured on plastic and laminin 521 (LM-521) has been studied. It was shown for the first time that LM-521 can increase the sensitivity of tumor cells to 5FU. Based on the analysis of the transcriptome and proteome, a possible mechanism of the observed effect of LM-521 on HT29 cell viability was proposed. The interaction of β1-containing integrins on the cell surface with LM-521 can activate the FAK/PI3K/Akt signaling pathways, promote phosphorylation of the YAP transcription coactivator and its binding to a complex with the 14-3-3σ protein. The formation of such complex leads to the YAP retention in the cytoplasm, prevents its transport to the nucleus and the activation of anti-apoptotic gene transcription. apoptosis, β1 integrin, colorectal cancer, laminin 521 (laminin-11), regorafenib, 5-fluorouracil, HT29, ITGB1, LAMA5, YAP, SFN, 14-3-3σ The study was funded by the Russian Science Foundation (Project 17-14-01338). |
| Databáze: | OpenAIRE |
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