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

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Frontiers in Molecular Biosciences Pub Date : 2024-07-30 DOI:10.3389/fmolb.2024.1359956

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

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Abstract

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.

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人胶质母细胞瘤干细胞中钙蛋白hcast 3-25的表达和钙蛋白酶/钙蛋白系统的活性：hcast 3-25可能参与细胞分化

胶质母细胞瘤（GBM）是恶性程度最高的脑肿瘤，其特点是由干细胞（GSCs）组成的细胞异质性，具有侵袭性。钙蛋白酶/钙司他丁（calp/cast）蛋白水解系统参与了关键的生理过程和癌症进展。在这项工作中，我们展示了 hcast 3-25（一种不含抑制单位的Ⅲ型钙蛋白变体）和该系统成员在几种患者衍生的 GSC 中的表达谱，探索了 hcast 3-25 与钙蛋白酶的激活/活性之间的关系。每种 GSC 都显示出独特的钙蛋白酶/钙蛋白酶 mRNA 和蛋白质表达模式，其中 hcast 3-25 的表达量最少。分化促进了除 hcast 3-25 mRNA 之外的所有钙蛋白/钙蛋白系统成分的上调，而 hcast 3-25 mRNA 的增减则取决于个体 GSC 的培养。将hcast 3-25-V5转染到两个选定的GSC中表明，hcast 3-25能有效地与钙蛋白酶结合，支持消化选定的钙蛋白酶靶标。Hcast 3-25可能会影响干细胞状态，促进分化，降低侵袭性表型。

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来源期刊

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.