Deregulation of protein phosphatase 2A inhibitor SET is associated with malignant progression in breast cancer

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 carcin...

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Published in:Scientific reports 2021-07, Vol.11 (1), p.14238-14238, Article 14238
Main Authors: Tozuka, Katsunori, Wongsirisin, Pattama, Nagai, Shigenori E., Kobayashi, Yasuhito, Kanno, Miki, Kubo, Kazuyuki, Takai, Ken, Inoue, Kenichi, Matsumoto, Hiroshi, Shimizu, Yoshihito, Suganuma, Masami
Format: Article
Language:English
Subjects:
631/67
631/80
Biomarkers
Breast cancer
Breast carcinoma
Deregulation
Humanities and Social Sciences
Invasiveness
Lymph nodes
Metastases
Metastasis
multidisciplinary
Oct-4 protein
Patients
Phosphatase
Phosphoprotein phosphatase
Protein phosphatase
Science
Science (multidisciplinary)
siRNA
Tumors
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-93620-y