Expression of calpastatin hcast 3-25 and activity of the calpain/calpastatin system in human glioblastoma stem cells: possible involvement of hcast 3-25 in cell differentiation

Sonia Spinelli; Sonia Spinelli; Federica Barbieri; Federica Barbieri; Monica Averna; Tullio Florio; Tullio Florio; Marco Pedrazzi; Beatrice F. Tremonti; Michela Capraro; Roberta De Tullio

doi:10.3389/fmolb.2024.1359956

Frontiers in Molecular Biosciences (Jul 2024)

Expression of calpastatin hcast 3-25 and activity of the calpain/calpastatin system in human glioblastoma stem cells: possible involvement of hcast 3-25 in cell differentiation

Sonia Spinelli,
Sonia Spinelli,
Federica Barbieri,
Federica Barbieri,
Monica Averna,
Tullio Florio,
Tullio Florio,
Marco Pedrazzi,
Beatrice F. Tremonti,
Michela Capraro,
Roberta De Tullio

Affiliations

Sonia Spinelli: IRCCS Istituto Giannina Gaslini, Laboratory of Molecular Nephrology, Genova, Italy
Sonia Spinelli: Department of Experimental Medicine (DIMES), Section of Biochemistry, University of Genova, Genova, Italy
Federica Barbieri: Department of Internal Medicine (DIMI), Section of Pharmacology, University of Genova, Genova, Italy
Federica Barbieri: IRCCS Ospedale Policlinico San Martino, Genova, Italy
Monica Averna: Department of Experimental Medicine (DIMES), Section of Biochemistry, University of Genova, Genova, Italy
Tullio Florio: Department of Internal Medicine (DIMI), Section of Pharmacology, University of Genova, Genova, Italy
Tullio Florio: IRCCS Ospedale Policlinico San Martino, Genova, Italy
Marco Pedrazzi: Department of Experimental Medicine (DIMES), Section of Biochemistry, University of Genova, Genova, Italy
Beatrice F. Tremonti: Department of Internal Medicine (DIMI), Section of Pharmacology, University of Genova, Genova, Italy
Michela Capraro: Department of Experimental Medicine (DIMES), Section of Biochemistry, University of Genova, Genova, Italy
Roberta De Tullio: Department of Experimental Medicine (DIMES), Section of Biochemistry, University of Genova, Genova, Italy

DOI: https://doi.org/10.3389/fmolb.2024.1359956
Journal volume & issue: Vol. 11

Abstract

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Glioblastoma (GBM) is the most malignant brain tumor, characterized by cell heterogeneity comprising stem cells (GSCs) responsible for aggressiveness. The calpain/calpastatin (calp/cast) proteolytic system is involved in critical physiological processes and cancer progression. In this work we showed the expression profile of hcast 3-25 (a Type III calpastatin variant devoid of inhibitory units) and the members of the system in several patient-derived GSCs exploring the relationship between hcast 3-25 and activation/activity of calpains. Each GSC shows a peculiar calp/cast mRNA and protein expression pattern, and hcast 3-25 is the least expressed. Differentiation promotes upregulation of all the calp/cast system components except hcast 3-25 mRNA, which increased or decreased depending on individual GSC culture. Transfection of hcast 3-25-V5 into two selected GSCs indicated that hcast 3-25 effectively associates with calpains, supporting the digestion of selected calpain targets. Hcast 3-25 possibly affects the stem state promoting a differentiated, less aggressive phenotype.

Published in Frontiers in Molecular Biosciences

ISSN: 2296-889X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.frontiersin.org/journals/molecular-biosciences

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