Effect of IGFBP6 Knockdown on Proteins Regulating Exosome Synthesis and Secretion in MDA-MB-231 Cell Line

Bull Exp Biol Med. 2023 May;175(1):157-161. doi: 10.1007/s10517-023-05828-9. Epub 2023 Jun 19.

Abstract

One of the potential causes of cancer recurrence is disruption of the cell-cell communication in the primary tumors that is realized, among other things, through secretion and uptake of exosomes by cells. Low expression of the IGFBP6 gene (insulin-like growth factor binding protein 6) is associated with a high recurrence rate and can serve as a prognostic marker of luminal breast cancer. The knockdown of the IGFBP6 gene leads to significant changes in lipid metabolism. We performed a quantitative analysis of both exosomes and proteins involved in the mechanism of their biogenesis. Changes in the expression profile of mRNAs and their proteins responsible for the synthesis and secretion of exosomes were revealed. We showed a decrease in the expression of the of the VPS28 gene mRNA (vacuolar protein sorting-associated protein 28) and the corresponding protein by 2.3 and 5.6 times, respectively. The secretion of exosomes by MDA-MB-231 cells with IGFBP6 knockdown decreased by 2 times. We discussed a mechanism of disruption of cell-cell communication.

Keywords: IGFBP6; MDA-MB-231; breast cancer; exosomes.

MeSH terms

  • Cell Line, Tumor
  • Exosomes* / genetics
  • Exosomes* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Insulin-Like Growth Factor Binding Protein 6* / genetics
  • Insulin-Like Growth Factor Binding Protein 6* / metabolism
  • MDA-MB-231 Cells
  • Neoplasm Recurrence, Local / genetics

Substances

  • Insulin-Like Growth Factor Binding Protein 6