To understand the mechanism underlying
metastasis, identification of a mechanism-based and common
biomarker for circulating tumour cells (CTCs) in heterogenous
breast cancer is needed. SET, an endogenous inhibitor of
protein phosphatase 2A, was overexpressed in all subtypes of invasive
breast carcinoma tissues. Treatment with SET-targeted siRNAs reduced the motility of MCF-7 and MDA-MB-231 cells in transwell assay. SET knockdown reduced the number of mammospheres by 60-70% in MCF-7 and MDA-MB-231 cells, which was associated with the downregulation of OCT4 and SLUG. Hence, we analysed the presence of SET-expressing CTCs (SET-CTCs) in 24
breast cancer patients. CTCs were enriched using a size-based method and then immunocytochemically analysed using an anti-SET antibody. SET-CTCs were detected in 6/6 (100%) patients with recurrent
breast cancer with a median value of 12 (12 cells/3 mL blood), and in 13/18 (72.2%) patients with stage I-III
breast cancer with a median value of 2.5, while the median value of healthy controls was 0. Importantly, high numbers of SET-CTCs were correlated with
lymph node metastasis in patients with stage I-III disease. Our results indicate that SET contributes to
breast cancer progression and can act as a potential
biomarker of CTCs for the detection of
metastasis.