PDSS2 Promotes Epithelial-Mesenchymal Transition and Angiogenesis in Breast Cancer Cells by Activating the NF-κB Pathway

Abstract

Objectives: Prenyl diphosphate synthase subunit 2 (PDSS2) has been closely linked to malignant behaviors in several cancers, including gastric cancer, melanoma and lung cancer, but its significance and mechanism in breast cancer (BC) are not still clarified. The purpose of this study was to look into the function of PDSS2 in BC and elucidate how it affects the survival of BC patients. Methods: The tumor tissues (BC) and histologically normal tissues (Normal) were obtained from 40 BC patients. BC cell lines HCC1937, MCF-7 and human normal breast cells MCF10A were cultured. Western blotting, Quantitative real-time polymerase chain reaction (qRT-PCR), and bioinformatics were performed to detect the PDSS2 expression in BC tissues and cells. Plasmids carrying PDSS2 siRNA (si-PDSS2) or overexpression plasmid (oe-PDSS2) were transferred into MCF-7 and HCC1937 cells. Functional experiments were conducted to determine the impact of PDSS2 on BC cell invasion, migration, and angiogenesis. In addition, the western blot determined the protein expression of Vimentin, N-cadherin, E-cadherin, p-IKBα, p-P65, P65, and p-IKBα proteins. Results: In BC tissues and cells, PDSS2 expression was notably elevated (p < 0.01), and worse overall survival (OS) were associated with the high PDSS2 expression (p < 0.01). Besides, overexpression of PDSS2 significantly increased the invasion, migration and tube formation ability of BC cells and encouraged epithelial-mesenchymal transition (EMT) (p < 0.01). However, PDSS2 knockdown inhibited cancer cell progression (p < 0.01). Moreover, PDSS2 enhanced the phosphorylation of the NF-κB pathway proteins IKBα and P65 (p < 0.01). Conclusions: PDSS2 can promote the invasion, migration, angiogenesis and EMT of BC cells through stimulation of the NF-κB pathway.