A novel mechanism of plasminogen activation in epithelial and mesenchymal cells

Moamen Bydoun; Andra Sterea; Ian C.G. Weaver; Alamelu Dharini Bharadwaj; David M. Waisman

doi:10.1038/s41598-018-32433-y

A novel mechanism of plasminogen activation in epithelial and mesenchymal cells

Moamen Bydoun, Andra Sterea, Ian C.G. Weaver, Alamelu Dharini Bharadwaj, David M. Waisman

Medicine

Medicine

Résultat de recherche: Article › examen par les pairs

23 Citations (Scopus)

Résumé

Cancer dissemination is initiated by the movement of cells into the vasculature which has been reported to be triggered by EMT (epithelial to mesenchymal transition). Cellular dissemination also requires proteases that remodel the extracellular matrix. The protease, plasmin is a prominent player in matrix remodeling and invasion. Despite the contribution of both EMT and the plasminogen activation (PA) system to cell dissemination, these processes have never been functionally linked. We reveal that canonical Smad-dependent TGFβ1 signaling and FOXC2-mediated PI3K signaling in cells undergoing EMT reciprocally modulate plasminogen activation partly by regulating the plasminogen receptor, S100A10 and the plasminogen activation inhibitor, PAI-1. Plasminogen activation and plasminogen-dependent invasion were more prominent in epithelial-like cells and were partly dictated by the expression of S100A10 and PAI-1.

Langue d'origine	English
Numéro d'article	14091
Journal	Scientific Reports
Volume	8
Numéro de publication	1
DOI	https://doi.org/10.1038/s41598-018-32433-y
Statut de publication	Published - déc. 1 2018

Note bibliographique

Funding Information:
The study was supported by the Canadian Institutes of health Research (CIHR) and Cancer Research Society. MB is supported through the cancer research training program (CRTP) administered by the Beatrice Hunter Cancer Research Institute (BHCRI) and funded by the Canadian Institute of Health Research (CIHR), Terry Fox Research Institute (TFRI), Cancer Care Nova Scotia, Dalhousie Medical Research Foundation (DMRF) and the Canadian Cancer Society Nova Scotia Division.

Publisher Copyright:
© 2018, The Author(s).

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General

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Journal Article
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10.1038/s41598-018-32433-y

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abstract = "Cancer dissemination is initiated by the movement of cells into the vasculature which has been reported to be triggered by EMT (epithelial to mesenchymal transition). Cellular dissemination also requires proteases that remodel the extracellular matrix. The protease, plasmin is a prominent player in matrix remodeling and invasion. Despite the contribution of both EMT and the plasminogen activation (PA) system to cell dissemination, these processes have never been functionally linked. We reveal that canonical Smad-dependent TGFβ1 signaling and FOXC2-mediated PI3K signaling in cells undergoing EMT reciprocally modulate plasminogen activation partly by regulating the plasminogen receptor, S100A10 and the plasminogen activation inhibitor, PAI-1. Plasminogen activation and plasminogen-dependent invasion were more prominent in epithelial-like cells and were partly dictated by the expression of S100A10 and PAI-1.",

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N2 - Cancer dissemination is initiated by the movement of cells into the vasculature which has been reported to be triggered by EMT (epithelial to mesenchymal transition). Cellular dissemination also requires proteases that remodel the extracellular matrix. The protease, plasmin is a prominent player in matrix remodeling and invasion. Despite the contribution of both EMT and the plasminogen activation (PA) system to cell dissemination, these processes have never been functionally linked. We reveal that canonical Smad-dependent TGFβ1 signaling and FOXC2-mediated PI3K signaling in cells undergoing EMT reciprocally modulate plasminogen activation partly by regulating the plasminogen receptor, S100A10 and the plasminogen activation inhibitor, PAI-1. Plasminogen activation and plasminogen-dependent invasion were more prominent in epithelial-like cells and were partly dictated by the expression of S100A10 and PAI-1.

AB - Cancer dissemination is initiated by the movement of cells into the vasculature which has been reported to be triggered by EMT (epithelial to mesenchymal transition). Cellular dissemination also requires proteases that remodel the extracellular matrix. The protease, plasmin is a prominent player in matrix remodeling and invasion. Despite the contribution of both EMT and the plasminogen activation (PA) system to cell dissemination, these processes have never been functionally linked. We reveal that canonical Smad-dependent TGFβ1 signaling and FOXC2-mediated PI3K signaling in cells undergoing EMT reciprocally modulate plasminogen activation partly by regulating the plasminogen receptor, S100A10 and the plasminogen activation inhibitor, PAI-1. Plasminogen activation and plasminogen-dependent invasion were more prominent in epithelial-like cells and were partly dictated by the expression of S100A10 and PAI-1.

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A novel mechanism of plasminogen activation in epithelial and mesenchymal cells

Résumé

Note bibliographique

ASJC Scopus Subject Areas

PubMed: MeSH publication types

ODD de l’ONU

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