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

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

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.662843

DOI=10.3389/fgene.2021.662843

ISSN=1664-8021

ABSTRACT=<p>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 <italic>ELOVL5</italic> and <italic>IGFBP6</italic> 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 <italic>ELOVL5</italic> and <italic>IGFBP6</italic> genes. The knockdown of <italic>ELOVL5</italic> and <italic>IGFBP6</italic> genes was found to lead to a strong increase in the expression of the matrix metalloproteinase (MMP) <italic>MMP1</italic>. 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 <italic>ELOVL5</italic> and <italic>IGFBP6</italic> 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 <italic>CDH11</italic> 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 <italic>ELOVL5</italic> and <italic>IGFBP6</italic> genes. Thus, the obtained data indicate that malignant breast tumors with reduced expression of the <italic>ELOVL5</italic> and <italic>IGFBP6</italic> genes can metastasize with a higher probability due to a more efficient invasion of tumor cells.</p>