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

Abstract 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 brea...

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Autores principales:	Katsunori Tozuka, Pattama Wongsirisin, Shigenori E. Nagai, Yasuhito Kobayashi, Miki Kanno, Kazuyuki Kubo, Ken Takai, Kenichi Inoue, Hiroshi Matsumoto, Yoshihito Shimizu, Masami Suganuma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ed41bad432af419a9baf36baf65e40ba
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spelling	oai:doaj.org-article:ed41bad432af419a9baf36baf65e40ba2021-12-02T15:39:59ZDeregulation of protein phosphatase 2A inhibitor SET is associated with malignant progression in breast cancer10.1038/s41598-021-93620-y2045-2322https://doaj.org/article/ed41bad432af419a9baf36baf65e40ba2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93620-yhttps://doaj.org/toc/2045-2322Abstract 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.Katsunori TozukaPattama WongsirisinShigenori E. NagaiYasuhito KobayashiMiki KannoKazuyuki KuboKen TakaiKenichi InoueHiroshi MatsumotoYoshihito ShimizuMasami SuganumaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katsunori Tozuka Pattama Wongsirisin Shigenori E. Nagai Yasuhito Kobayashi Miki Kanno Kazuyuki Kubo Ken Takai Kenichi Inoue Hiroshi Matsumoto Yoshihito Shimizu Masami Suganuma Deregulation of protein phosphatase 2A inhibitor SET is associated with malignant progression in breast cancer
description	Abstract 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.
format	article
author	Katsunori Tozuka Pattama Wongsirisin Shigenori E. Nagai Yasuhito Kobayashi Miki Kanno Kazuyuki Kubo Ken Takai Kenichi Inoue Hiroshi Matsumoto Yoshihito Shimizu Masami Suganuma
author_facet	Katsunori Tozuka Pattama Wongsirisin Shigenori E. Nagai Yasuhito Kobayashi Miki Kanno Kazuyuki Kubo Ken Takai Kenichi Inoue Hiroshi Matsumoto Yoshihito Shimizu Masami Suganuma
author_sort	Katsunori Tozuka
title	Deregulation of protein phosphatase 2A inhibitor SET is associated with malignant progression in breast cancer
title_short	Deregulation of protein phosphatase 2A inhibitor SET is associated with malignant progression in breast cancer
title_full	Deregulation of protein phosphatase 2A inhibitor SET is associated with malignant progression in breast cancer
title_fullStr	Deregulation of protein phosphatase 2A inhibitor SET is associated with malignant progression in breast cancer
title_full_unstemmed	Deregulation of protein phosphatase 2A inhibitor SET is associated with malignant progression in breast cancer
title_sort	deregulation of protein phosphatase 2a inhibitor set is associated with malignant progression in breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ed41bad432af419a9baf36baf65e40ba
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Deregulation of protein phosphatase 2A inhibitor SET is associated with malignant progression in breast cancer

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