Nuclear Syndecan-1 Regulates Epithelial-Mesenchymal Plasticity in Tumor Cells

Tumor cells undergoing epithelial-mesenchymal transition (EMT) lose cell surface adhesion molecules and gain invasive and metastatic properties. EMT is a plastic process and tumor cells may shift between different epithelial-mesenchymal states during metastasis. However, how this is regulated is not...

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Main Authors: Ashish Kumar-Singh, Malgorzata Maria Parniewska, Nikolina Giotopoulou, Joman Javadi, Wenwen Sun, Tünde Szatmári, Katalin Dobra, Anders Hjerpe, Jonas Fuxe
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/10/6/521
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author Ashish Kumar-Singh
Malgorzata Maria Parniewska
Nikolina Giotopoulou
Joman Javadi
Wenwen Sun
Tünde Szatmári
Katalin Dobra
Anders Hjerpe
Jonas Fuxe
author_facet Ashish Kumar-Singh
Malgorzata Maria Parniewska
Nikolina Giotopoulou
Joman Javadi
Wenwen Sun
Tünde Szatmári
Katalin Dobra
Anders Hjerpe
Jonas Fuxe
author_sort Ashish Kumar-Singh
collection DOAJ
description Tumor cells undergoing epithelial-mesenchymal transition (EMT) lose cell surface adhesion molecules and gain invasive and metastatic properties. EMT is a plastic process and tumor cells may shift between different epithelial-mesenchymal states during metastasis. However, how this is regulated is not fully understood. Syndecan-1 (SDC1) is the major cell surface proteoglycan in epithelial cells and has been shown to regulate carcinoma progression and EMT. Recently, it was discovered that SDC1 translocates into the cell nucleus in certain tumor cells. Nuclear SDC1 inhibits cell proliferation, but whether nuclear SDC1 contributes to the regulation of EMT is not clear. Here, we report that loss of nuclear SDC1 is associated with cellular elongation and an E-cadherin-to-N-cadherin switch during TGF-β1-induced EMT in human A549 lung adenocarcinoma cells. Further studies showed that nuclear translocation of SDC1 contributed to the repression of mesenchymal and invasive properties of human B6FS fibrosarcoma cells. The results demonstrate that nuclear translocation contributes to the capacity of SDC1 to regulate epithelial-mesenchymal plasticity in human tumor cells and opens up to mechanistic studies to elucidate the mechanisms involved.
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spelling doaj.art-dd0786ef4bf34fb7b32bda46a35f67512023-11-21T23:42:55ZengMDPI AGBiology2079-77372021-06-0110652110.3390/biology10060521Nuclear Syndecan-1 Regulates Epithelial-Mesenchymal Plasticity in Tumor CellsAshish Kumar-Singh0Malgorzata Maria Parniewska1Nikolina Giotopoulou2Joman Javadi3Wenwen Sun4Tünde Szatmári5Katalin Dobra6Anders Hjerpe7Jonas Fuxe8Department of Laboratory Medicine, Karolinska Institutet, Division of Pathology, SE-14186 Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Division of Pathology, SE-14186 Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Division of Pathology, SE-14186 Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Division of Pathology, SE-14186 Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Division of Pathology, SE-14186 Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Division of Pathology, SE-14186 Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Division of Pathology, SE-14186 Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Division of Pathology, SE-14186 Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Division of Pathology, SE-14186 Stockholm, SwedenTumor cells undergoing epithelial-mesenchymal transition (EMT) lose cell surface adhesion molecules and gain invasive and metastatic properties. EMT is a plastic process and tumor cells may shift between different epithelial-mesenchymal states during metastasis. However, how this is regulated is not fully understood. Syndecan-1 (SDC1) is the major cell surface proteoglycan in epithelial cells and has been shown to regulate carcinoma progression and EMT. Recently, it was discovered that SDC1 translocates into the cell nucleus in certain tumor cells. Nuclear SDC1 inhibits cell proliferation, but whether nuclear SDC1 contributes to the regulation of EMT is not clear. Here, we report that loss of nuclear SDC1 is associated with cellular elongation and an E-cadherin-to-N-cadherin switch during TGF-β1-induced EMT in human A549 lung adenocarcinoma cells. Further studies showed that nuclear translocation of SDC1 contributed to the repression of mesenchymal and invasive properties of human B6FS fibrosarcoma cells. The results demonstrate that nuclear translocation contributes to the capacity of SDC1 to regulate epithelial-mesenchymal plasticity in human tumor cells and opens up to mechanistic studies to elucidate the mechanisms involved.https://www.mdpi.com/2079-7737/10/6/521syndecan-1SDC1nuclear translocationepithelial-mesenchymal transitionplasticityTGF-β1
spellingShingle Ashish Kumar-Singh
Malgorzata Maria Parniewska
Nikolina Giotopoulou
Joman Javadi
Wenwen Sun
Tünde Szatmári
Katalin Dobra
Anders Hjerpe
Jonas Fuxe
Nuclear Syndecan-1 Regulates Epithelial-Mesenchymal Plasticity in Tumor Cells
Biology
syndecan-1
SDC1
nuclear translocation
epithelial-mesenchymal transition
plasticity
TGF-β1
title Nuclear Syndecan-1 Regulates Epithelial-Mesenchymal Plasticity in Tumor Cells
title_full Nuclear Syndecan-1 Regulates Epithelial-Mesenchymal Plasticity in Tumor Cells
title_fullStr Nuclear Syndecan-1 Regulates Epithelial-Mesenchymal Plasticity in Tumor Cells
title_full_unstemmed Nuclear Syndecan-1 Regulates Epithelial-Mesenchymal Plasticity in Tumor Cells
title_short Nuclear Syndecan-1 Regulates Epithelial-Mesenchymal Plasticity in Tumor Cells
title_sort nuclear syndecan 1 regulates epithelial mesenchymal plasticity in tumor cells
topic syndecan-1
SDC1
nuclear translocation
epithelial-mesenchymal transition
plasticity
TGF-β1
url https://www.mdpi.com/2079-7737/10/6/521
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