Abstract
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 14-3-3 σ 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.
Original language | English |
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Pages (from-to) | 73-79 |
Number of pages | 7 |
Journal | Biotekhnologiya |
Volume | 35 |
Issue number | 6 |
DOIs | |
State | Published - 2019 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© State Research Institute for Genetics and Selection of Industrial Microorganisms.
Keywords
- 14-3-3 σ
- 5-fluorouracil
- Apoptosis
- Colorectal cancer
- HT29
- ITGB1
- LAMA5
- Laminin 521 (laminin-11)
- Regorafenib
- SFN
- YAP
- ß1 integrin