Laminin 521 modulates the sytotoxic effect of 5-fluorouracil on colorectal cancer ht29 cells

M. P. Raigorodskaya, A. Turchinovich, I. M. Tsypina, V. G. Zgoda, S. V. Nikulin, D. V. Maltseva

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)73-79
Number of pages7
JournalBiotekhnologiya
Volume35
Issue number6
DOIs
StatePublished - 2019
Externally publishedYes

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

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