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Laminin 521 Modulates the Сytotoxic Effect of 5-Fluorouracil on HT29 Colorectal Cancer Cells

Laminin 521 Modulates the Сytotoxic Effect of 5-Fluorouracil on HT29 Colorectal Cancer Cells The cytotoxic effect of 5-fluorouracil (5FU) and regorafenib (RF), drugs with different mechanisms of action used to treat colorectal cancer, on an HT29 cell line cultured on plastic or laminin 521 (LM-521) has been studied. It is first shown that LM-521 can increase the sensitivity of tumor cells to 5FU. A possible mechanism of the observed effect of LM-521 on the HT29 cell viability is proposed based on transcriptome and proteome analysis. The interaction of β1-containing integrins on the cell surface with LM-521 can activate the FAK/PI3K/Akt signaling pathways and promote phosphorylation of the YAP transcription coactivator and its binding to the complex with the 14-3-3σ protein. The formation of this complex leads to YAP retention in the cytoplasm and prevents its transport to the nucleus and the activation of antiapoptotic gene transcription. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Applied Biochemistry and Microbiology Springer Journals

Laminin 521 Modulates the Сytotoxic Effect of 5-Fluorouracil on HT29 Colorectal Cancer Cells

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References (25)

Publisher
Springer Journals
Copyright
Copyright © Pleiades Publishing, Inc. 2020. ISSN 0003-6838, Applied Biochemistry and Microbiology, 2020, Vol. 56, No. 8, pp. 870–874. © Pleiades Publishing, Inc., 2020. Russian Text © The Author(s), 2019, published in Biotekhnologiya, 2019, Vol. 35, No. 6, pp. 73–79.
ISSN
0003-6838
eISSN
1608-3024
DOI
10.1134/S0003683820080074
Publisher site
See Article on Publisher Site

Abstract

The cytotoxic effect of 5-fluorouracil (5FU) and regorafenib (RF), drugs with different mechanisms of action used to treat colorectal cancer, on an HT29 cell line cultured on plastic or laminin 521 (LM-521) has been studied. It is first shown that LM-521 can increase the sensitivity of tumor cells to 5FU. A possible mechanism of the observed effect of LM-521 on the HT29 cell viability is proposed based on transcriptome and proteome analysis. The interaction of β1-containing integrins on the cell surface with LM-521 can activate the FAK/PI3K/Akt signaling pathways and promote phosphorylation of the YAP transcription coactivator and its binding to the complex with the 14-3-3σ protein. The formation of this complex leads to YAP retention in the cytoplasm and prevents its transport to the nucleus and the activation of antiapoptotic gene transcription.

Journal

Applied Biochemistry and MicrobiologySpringer Journals

Published: Dec 1, 2020

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