Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 870-874 |
| Number of pages | 5 |
| Journal | Applied Biochemistry and Microbiology |
| Volume | 56 |
| Issue number | 8 |
| DOIs | |
| State | Published - Dec 2020 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2020, Pleiades Publishing, Inc.
Funding
The proteome analysis was carried out on the equipment of Human Proteome Center for Common Use (IBMKh).
| Funders | Funder number |
|---|---|
| Human Proteome Center for Common Use |
Keywords
- 14-3-3σ
- 5-fluorouracil
- HT29
- ITGB1
- LAMA5
- SFN
- YAP
- apoptosis
- colorectal cancer
- laminin 521 (laminin-11)
- regorafenib
- β1 integrin
