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 |
|---|---|
| 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.
Funding
The study was funded by the Russian Science Foundation (Project 17-14-01338).
| Funders | Funder number |
|---|---|
| Russian Science Foundation | 17-14-01338 |
Keywords
- 14-3-3 σ
- 5-fluorouracil
- Apoptosis
- Colorectal cancer
- HT29
- ITGB1
- LAMA5
- Laminin 521 (laminin-11)
- Regorafenib
- SFN
- YAP
- ß1 integrin
