Effect of the Expression of ELOVL5 and IGFBP6 Genes on the Metastatic Potential of Breast Cancer Cells

Sergey Nikulin, Galina Zakharova, Andrey Poloznikov, Maria Raigorodskaya, Daniel Wicklein, Udo Schumacher, Stepan Nersisyan, Jonas Bergquist, Georgy Bakalkin, Lidiia Astakhova, Alexander Tonevitsky

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Breast cancer (BC) is the leading cause of death from malignant neoplasms among women worldwide, and metastatic BC presents the biggest problems for treatment. Previously, it was shown that lower expression of ELOVL5 and IGFBP6 genes is associated with a higher risk of the formation of distant metastases in BC. In this work, we studied the change in phenotypical traits, as well as in the transcriptomic and proteomic profiles of BC cells as a result of the stable knockdown of ELOVL5 and IGFBP6 genes. The knockdown of ELOVL5 and IGFBP6 genes was found to lead to a strong increase in the expression of the matrix metalloproteinase (MMP) MMP1. These results were in good agreement with the correlation analysis of gene expression in tumor samples from patients and were additionally confirmed by zymography. The knockdown of ELOVL5 and IGFBP6 genes was also discovered to change the expression of a group of genes involved in the formation of intercellular contacts. In particular, the expression of the CDH11 gene was markedly reduced, which also complies with the correlation analysis. The spheroid formation assay showed that intercellular adhesion decreased as a result of the knockdown of the ELOVL5 and IGFBP6 genes. Thus, the obtained data indicate that malignant breast tumors with reduced expression of the ELOVL5 and IGFBP6 genes can metastasize with a higher probability due to a more efficient invasion of tumor cells.

Original languageEnglish
Article number662843
JournalFrontiers in Genetics
Volume12
DOIs
StatePublished - 2 Jun 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© Copyright © 2021 Nikulin, Zakharova, Poloznikov, Raigorodskaya, Wicklein, Schumacher, Nersisyan, Bergquist, Bakalkin, Astakhova and Tonevitsky.

Keywords

  • ELOVL5
  • IGFBP6
  • MDA-MB-231
  • breast cancer
  • cell–cell contacts
  • matrix metalloproteinases

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