Data_Sheet_1_Effect of the Expression of ELOVL5 and IGFBP6 Genes on the Metastatic Potential of Breast Cancer Cells.PDF

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.

乳腺癌（Breast cancer, BC）是全球范围内女性恶性肿瘤相关死亡的首要病因，而转移性乳腺癌仍是当前临床治疗面临的最大难题。此前已有研究证实，ELOVL5与IGFBP6基因的低表达与乳腺癌患者发生远处转移的风险升高显著相关。本研究针对ELOVL5与IGFBP6基因稳定敲低后的乳腺癌细胞，分析其表型特征以及转录组、蛋白质组表达谱的变化。研究发现，敲低ELOVL5与IGFBP6基因可显著上调基质金属蛋白酶（matrix metalloproteinase, MMP）MMP1的表达。该结果与患者肿瘤样本的基因表达相关性分析结果高度吻合，并通过酶谱分析法得到了进一步验证。此外，敲低ELOVL5与IGFBP6基因还可改变一组参与细胞间连接形成的基因的表达水平；具体而言，CDH11基因的表达水平显著下调，这一结果同样契合相关性分析结论。球体形成实验结果显示，敲低ELOVL5与IGFBP6基因可降低细胞间黏附能力。综上，本研究数据表明，ELOVL5与IGFBP6基因低表达的恶性乳腺肿瘤，可通过增强肿瘤细胞的侵袭能力，获得更高的转移潜能。