SerpinB3 Upregulates Low-Density Lipoprotein Receptor-Related Protein (LRP) Family Members, Leading to Wnt Signaling Activation and Increased Cell Survival and Invasiveness
Abnormal activation of the Wnt-β-catenin signaling cascade is involved in tumor growth and dissemination. SerpinB3 has been shown to induce β-catenin, and both molecules are overexpressed in tumors, particularly in those with poor prognoses. The aim of this study was to evaluate the ability of Serpi...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2023-05-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/12/6/771 |
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| author | Santina Quarta Andrea Cappon Cristian Turato Mariagrazia Ruvoletto Stefania Cannito Gianmarco Villano Alessandra Biasiolo Maristella Maggi Francesca Protopapa Loris Bertazza Silvano Fasolato Maurizio Parola Patrizia Pontisso |
| author_facet | Santina Quarta Andrea Cappon Cristian Turato Mariagrazia Ruvoletto Stefania Cannito Gianmarco Villano Alessandra Biasiolo Maristella Maggi Francesca Protopapa Loris Bertazza Silvano Fasolato Maurizio Parola Patrizia Pontisso |
| author_sort | Santina Quarta |
| collection | DOAJ |
| description | Abnormal activation of the Wnt-β-catenin signaling cascade is involved in tumor growth and dissemination. SerpinB3 has been shown to induce β-catenin, and both molecules are overexpressed in tumors, particularly in those with poor prognoses. The aim of this study was to evaluate the ability of SerpinB3 to modulate the Wnt pathway in liver cancer and in monocytic cells, the main type of inflammatory cells in the tumor microenvironment. The Wnt cascade, Wnt co-receptors, and low-density lipoprotein receptor-related protein (LRP) members were analyzed in different cell lines and human monocytes in the presence or absence of SerpinB3. The Wnt-β-catenin axis was also evaluated in liver tumors induced in mice with different extents of SeprinB3 expression. In monocytic cells, SerpinB3 induced a significant upregulation of Wnt-1/7, nuclear β-catenin, and c-Myc, which are associated with increased cell lifespan and proliferation. In liver tumors in mice, the expression of β-catenin was significantly correlated with the presence of SerpinB3. In hepatoma cells, Wnt co-receptors LRP-5/6 and LRP-1, implicated in cell survival and invasiveness, were upregulated by SerpinB3. The LRP pan-inhibitor RAP not only induced a decrease in LRP expression, but also a dose–dependent reduction in SerpinB3-induced invasiveness. In conclusion, SerpinB3 determines the activation of the Wnt canonical pathway and cell invasiveness through the upregulation of LRP family members. |
| first_indexed | 2024-03-11T02:45:45Z |
| format | Article |
| id | doaj.art-7b0a7c7106054584aa5d18b622756d12 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-11T02:45:45Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-7b0a7c7106054584aa5d18b622756d122023-11-18T09:22:21ZengMDPI AGBiology2079-77372023-05-0112677110.3390/biology12060771SerpinB3 Upregulates Low-Density Lipoprotein Receptor-Related Protein (LRP) Family Members, Leading to Wnt Signaling Activation and Increased Cell Survival and InvasivenessSantina Quarta0Andrea Cappon1Cristian Turato2Mariagrazia Ruvoletto3Stefania Cannito4Gianmarco Villano5Alessandra Biasiolo6Maristella Maggi7Francesca Protopapa8Loris Bertazza9Silvano Fasolato10Maurizio Parola11Patrizia Pontisso12Department of Medicine, University of Padova, 35128 Padua, ItalyDepartment of Medicine, University of Padova, 35128 Padua, ItalyDepartment of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyDepartment of Medicine, University of Padova, 35128 Padua, ItalyDepartment of Clinical and Biological Sciences, University of Torino, 10124 Turin, ItalyDepartment of Surgical, Oncological and Gastroenterological Sciences, University of Padova, 35128 Padua, ItalyDepartment of Medicine, University of Padova, 35128 Padua, ItalyDepartment of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyDepartment of Clinical and Biological Sciences, University of Torino, 10124 Turin, ItalyDepartment of Medicine, University of Padova, 35128 Padua, ItalyDepartment of Medicine, University of Padova, 35128 Padua, ItalyDepartment of Clinical and Biological Sciences, University of Torino, 10124 Turin, ItalyDepartment of Medicine, University of Padova, 35128 Padua, ItalyAbnormal activation of the Wnt-β-catenin signaling cascade is involved in tumor growth and dissemination. SerpinB3 has been shown to induce β-catenin, and both molecules are overexpressed in tumors, particularly in those with poor prognoses. The aim of this study was to evaluate the ability of SerpinB3 to modulate the Wnt pathway in liver cancer and in monocytic cells, the main type of inflammatory cells in the tumor microenvironment. The Wnt cascade, Wnt co-receptors, and low-density lipoprotein receptor-related protein (LRP) members were analyzed in different cell lines and human monocytes in the presence or absence of SerpinB3. The Wnt-β-catenin axis was also evaluated in liver tumors induced in mice with different extents of SeprinB3 expression. In monocytic cells, SerpinB3 induced a significant upregulation of Wnt-1/7, nuclear β-catenin, and c-Myc, which are associated with increased cell lifespan and proliferation. In liver tumors in mice, the expression of β-catenin was significantly correlated with the presence of SerpinB3. In hepatoma cells, Wnt co-receptors LRP-5/6 and LRP-1, implicated in cell survival and invasiveness, were upregulated by SerpinB3. The LRP pan-inhibitor RAP not only induced a decrease in LRP expression, but also a dose–dependent reduction in SerpinB3-induced invasiveness. In conclusion, SerpinB3 determines the activation of the Wnt canonical pathway and cell invasiveness through the upregulation of LRP family members.https://www.mdpi.com/2079-7737/12/6/771β-catenin signalingcell invasivenessWnt cell membrane co-receptors |
| spellingShingle | Santina Quarta Andrea Cappon Cristian Turato Mariagrazia Ruvoletto Stefania Cannito Gianmarco Villano Alessandra Biasiolo Maristella Maggi Francesca Protopapa Loris Bertazza Silvano Fasolato Maurizio Parola Patrizia Pontisso SerpinB3 Upregulates Low-Density Lipoprotein Receptor-Related Protein (LRP) Family Members, Leading to Wnt Signaling Activation and Increased Cell Survival and Invasiveness Biology β-catenin signaling cell invasiveness Wnt cell membrane co-receptors |
| title | SerpinB3 Upregulates Low-Density Lipoprotein Receptor-Related Protein (LRP) Family Members, Leading to Wnt Signaling Activation and Increased Cell Survival and Invasiveness |
| title_full | SerpinB3 Upregulates Low-Density Lipoprotein Receptor-Related Protein (LRP) Family Members, Leading to Wnt Signaling Activation and Increased Cell Survival and Invasiveness |
| title_fullStr | SerpinB3 Upregulates Low-Density Lipoprotein Receptor-Related Protein (LRP) Family Members, Leading to Wnt Signaling Activation and Increased Cell Survival and Invasiveness |
| title_full_unstemmed | SerpinB3 Upregulates Low-Density Lipoprotein Receptor-Related Protein (LRP) Family Members, Leading to Wnt Signaling Activation and Increased Cell Survival and Invasiveness |
| title_short | SerpinB3 Upregulates Low-Density Lipoprotein Receptor-Related Protein (LRP) Family Members, Leading to Wnt Signaling Activation and Increased Cell Survival and Invasiveness |
| title_sort | serpinb3 upregulates low density lipoprotein receptor related protein lrp family members leading to wnt signaling activation and increased cell survival and invasiveness |
| topic | β-catenin signaling cell invasiveness Wnt cell membrane co-receptors |
| url | https://www.mdpi.com/2079-7737/12/6/771 |
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