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The ANXA2/S100A10 Complex—Regulation of the Oncogenic Plasminogen Receptor

The generation of the serine protease plasmin is initiated by the binding of its zymogenic precursor, plasminogen, to cell surface receptors. The proteolytic activity of plasmin, generated at the cell surface, plays a crucial role in several physiological processes, including fibrinolysis, angiogene...

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Autores principales: Bharadwaj, Alamelu G., Kempster, Emma, Waisman, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698604/
https://www.ncbi.nlm.nih.gov/pubmed/34944416
http://dx.doi.org/10.3390/biom11121772
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author Bharadwaj, Alamelu G.
Kempster, Emma
Waisman, David M.
author_facet Bharadwaj, Alamelu G.
Kempster, Emma
Waisman, David M.
author_sort Bharadwaj, Alamelu G.
collection PubMed
description The generation of the serine protease plasmin is initiated by the binding of its zymogenic precursor, plasminogen, to cell surface receptors. The proteolytic activity of plasmin, generated at the cell surface, plays a crucial role in several physiological processes, including fibrinolysis, angiogenesis, wound healing, and the invasion of cells through both the basement membrane and extracellular matrix. The seminal observation by Albert Fischer that cancer cells, but not normal cells in culture, produce large amounts of plasmin formed the basis of current-day observations that plasmin generation can be hijacked by cancer cells to allow tumor development, progression, and metastasis. Thus, the cell surface plasminogen-binding receptor proteins are critical to generating plasmin proteolytic activity at the cell surface. This review focuses on one of the twelve well-described plasminogen receptors, S100A10, which, when in complex with its regulatory partner, annexin A2 (ANXA2), forms the ANXA2/S100A10 heterotetrameric complex referred to as AIIt. We present the theme that AIIt is the quintessential cellular plasminogen receptor since it regulates the formation and the destruction of plasmin. We also introduce the term oncogenic plasminogen receptor to define those plasminogen receptors directly activated during cancer progression. We then discuss the research establishing AIIt as an oncogenic plasminogen receptor-regulated during EMT and activated by oncogenes such as SRC, RAS, HIF1α, and PML-RAR and epigenetically by DNA methylation. We further discuss the evidence derived from animal models supporting the role of S100A10 in tumor progression and oncogenesis. Lastly, we describe the potential of S100A10 as a biomarker for cancer diagnosis and prognosis.
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spelling pubmed-86986042021-12-24 The ANXA2/S100A10 Complex—Regulation of the Oncogenic Plasminogen Receptor Bharadwaj, Alamelu G. Kempster, Emma Waisman, David M. Biomolecules Review The generation of the serine protease plasmin is initiated by the binding of its zymogenic precursor, plasminogen, to cell surface receptors. The proteolytic activity of plasmin, generated at the cell surface, plays a crucial role in several physiological processes, including fibrinolysis, angiogenesis, wound healing, and the invasion of cells through both the basement membrane and extracellular matrix. The seminal observation by Albert Fischer that cancer cells, but not normal cells in culture, produce large amounts of plasmin formed the basis of current-day observations that plasmin generation can be hijacked by cancer cells to allow tumor development, progression, and metastasis. Thus, the cell surface plasminogen-binding receptor proteins are critical to generating plasmin proteolytic activity at the cell surface. This review focuses on one of the twelve well-described plasminogen receptors, S100A10, which, when in complex with its regulatory partner, annexin A2 (ANXA2), forms the ANXA2/S100A10 heterotetrameric complex referred to as AIIt. We present the theme that AIIt is the quintessential cellular plasminogen receptor since it regulates the formation and the destruction of plasmin. We also introduce the term oncogenic plasminogen receptor to define those plasminogen receptors directly activated during cancer progression. We then discuss the research establishing AIIt as an oncogenic plasminogen receptor-regulated during EMT and activated by oncogenes such as SRC, RAS, HIF1α, and PML-RAR and epigenetically by DNA methylation. We further discuss the evidence derived from animal models supporting the role of S100A10 in tumor progression and oncogenesis. Lastly, we describe the potential of S100A10 as a biomarker for cancer diagnosis and prognosis. MDPI 2021-11-26 /pmc/articles/PMC8698604/ /pubmed/34944416 http://dx.doi.org/10.3390/biom11121772 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bharadwaj, Alamelu G.
Kempster, Emma
Waisman, David M.
The ANXA2/S100A10 Complex—Regulation of the Oncogenic Plasminogen Receptor
title The ANXA2/S100A10 Complex—Regulation of the Oncogenic Plasminogen Receptor
title_full The ANXA2/S100A10 Complex—Regulation of the Oncogenic Plasminogen Receptor
title_fullStr The ANXA2/S100A10 Complex—Regulation of the Oncogenic Plasminogen Receptor
title_full_unstemmed The ANXA2/S100A10 Complex—Regulation of the Oncogenic Plasminogen Receptor
title_short The ANXA2/S100A10 Complex—Regulation of the Oncogenic Plasminogen Receptor
title_sort anxa2/s100a10 complex—regulation of the oncogenic plasminogen receptor
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698604/
https://www.ncbi.nlm.nih.gov/pubmed/34944416
http://dx.doi.org/10.3390/biom11121772
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