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Recent Developments and Emerging Trends in Cytoskeletal and Cell Cycle Proteins

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A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Applied Biosciences and Bioengineering".

Deadline for manuscript submissions: closed (20 November 2021) | Viewed by 12839

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Special Issue Editors

Dr. Maciej Gagat

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Guest Editor

Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-092 Bydgoszcz, Poland
Interests: cytoskeleton; cell adhesion; cell-cell junctions; cell migration; endothelial dysfunction; cell death; cancer biomarkers
Special Issues, Collections and Topics in MDPI journals

Dr. Anna Klimaszewska-Wiśniewska

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Guest Editor

Department of Clinical Pathomorphology, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland
Interests: cytoskeleton; cell cycle; cell death; cancer biomarkers; dietary flavonoids

Special Issue Information

Dear Colleagues,

Since the cytoskeleton is an essential cellular component involved in virtually all cellular processes, it is therefore not surprising that, in recent years, cytoskeletal research has revolutionized cell biology and biomedicine. Our understanding on the intimate multiple-direction connection between this cellular structure, cell division, and other cytoskeleton-driven processes, in the context of both normal and abnormal cell function, is still increasing, and currently is directed toward the development of novel diagnostic and therapeutic strategies in various diseases such as cardiovascular disease and cancer. Likewise, an increasing amount of studies have implicated new and existing cell cycle regulators in many cellular transactions beyond cell cycle control, unveiling their involvement in more general processes such as DNA repair, transcription or cytoskeleton dynamics. It is clear that continued efforts in investigating these aspects of cell biology will further transform our understanding of diseases associated with cell cycle and cytoskeleton dysfunction, and may provide additional points of crosstalk between cell cycle machinery, cytoskeletons, and the associated proteins for more complex therapies.

This Special Issue is therefore devoted to presenting new trends in cytoskeletal and cell cycle research that specifically go beyond the traditional approach of the identification of new proteins and their functions, but also defining how these proteins interact and interfere with signalling pathways. This issue is also focused on basic studies of the alternative functions of cytoskeletal and cell cycle proteins in health and disease. Finally, presentations of new therapeutic agents, especially those originating from natural plant products, that act on these cellular targets are also highly welcome.

Keywords

cytoskeleton
cytoskeleton-associated proteins
cell cycle
new cell cycle players
non-canonical functions of cell cycle proteins
crosstalk between cell-cycle and cytoskeleton
DNA damage repair
DNA transcription
cancer
cancer biomarkers
cancer metastasis
epithelial-mesenchymal transition
mesenchymal-epithelial transition
cardiovascular disease
endothelial dysfunction
cell proliferation
cell death
apoptosis
mitotic catastrophe
autophagy
cell migration
cell adhesion
cell-cell junctions
live-cell imaging
drug targets
natural plant products
medical devices
treatment strategy

Published Papers (6 papers)

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Research

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17 pages, 4956 KiB

Open AccessArticle

Characterization of Cysteine Cathepsin Expression in the Central Nervous System of Aged Wild-Type and Cathepsin-Deficient Mice

by Denise M. T. Yu, Stephanie Dauth, Michael B. Margineanu, Valentina Snetkova, Maren Rehders, Silvia Jordans and Klaudia Brix

Appl. Sci. 2022, 12(5), 2608; https://0-doi-org.brum.beds.ac.uk/10.3390/app12052608 - 03 Mar 2022

Viewed by 2319

Abstract

The association of cathepsin proteases in neurobiology is increasingly recognized. Our previous studies indicated that cathepsin-K-deficient (Ctsk^−/−) mice have learning and memory impairments. Alterations in cathepsin expression are known to result in compensatory changes in levels of related cathepsins. To gain insight into the therapeutic usefulness of cathepsin inhibitors in aging individuals with osteoporosis or neurodegenerative diseases, we studied for variations in cathepsin expression and activity in aged (18–20 months) versus young (5–7 months) wild-type (WT) and cathepsin-deficient mice brains. There were age-dependent increases in cathepsin B, D, and L and cystatin C protein levels in various brain regions, mainly of WT and Ctsk^−/− mice. This corresponded with changes in activity levels of cathepsins B and L, but not cathepsin D. In contrast, very little age-dependent variation was observed in cathepsin-B- and cathepsin-L-deficient mouse brain, especially at the protein level. The observed alterations in cathepsin protein amounts and activity are likely contributing to changes in important aging-related processes such as autophagy. In addition, the results provide insight into the potential impact of cathepsin inhibitor therapy in aged individuals, as well as in long-term use of cathepsin inhibitor therapy. Full article

(This article belongs to the Special Issue Recent Developments and Emerging Trends in Cytoskeletal and Cell Cycle Proteins)

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26 pages, 5053 KiB

Open AccessArticle

Prognostic Significance of SATB1, SMAD3, Ezrin and β-Catenin in Patients with Pancreatic Adenocarcinoma

by Justyna Durślewicz, Anna Klimaszewska-Wiśniewska, Ewa Domanowska, Natalia Skoczylas-Makowska, Paulina Antosik, Wioletta Zielińska, Arkadiusz Gzil, Paulina Czajkowska, Klaudia Mikołajczyk and Dariusz Grzanka

Appl. Sci. 2022, 12(1), 306; https://0-doi-org.brum.beds.ac.uk/10.3390/app12010306 - 29 Dec 2021

Viewed by 1540

Abstract

The present study aimed to explore the role of SATB1, SMAD3, Ezrin and β-catenin as individual and combined biomarkers for the survival prediction in pancreatic adenocarcinoma (PAC). Notably, this study distinguished for the first time a potential prognostic value of SATB1 corresponding to its subcellular localization in PAC. Immunohistochemical staining on tissue macroarrays, as well as RNA-seq data from public sources, were investigated, and the results correlated with overall survival (OS) and clinicopathological features. The connectivity between the examined factors, as well as their common signaling pathways, were demonstrated by the functional enrichment analysis. Herein, the prognostic ability of cytoplasmic SATB1 in OS analysis was even superior to nuclear SATB1. Both staining patterns tended to have opposite roles in the prognosis of PAC: SATB1^c was an independent prognostic factor for poor OS, whereas SATB1ⁿ expression reached no statistical significance, but Kaplan–Meier curves separated patients with low expression and adverse prognosis from patients with high expression and favorable prognosis. High levels of SATB1 mRNA appeared as an independent prognostic indicator for better OS. Furthermore, individual expression of SMAD3 or Ezrin, as well as combined expression of SATB1/SMAD3/Ezrin/β-catenin, were associated with OS independently of conventional risk factors, both in our cohort and TCGA dataset. In our series, patients with tumors harboring combined expression of SATB1^n-high/SMAD3^low/Ezrin^low/β-catenin^low experienced the highest survival rates, while those with SATB1^c-present/SMAD3^high/Ezrin^high/β-catenin^high had the worst survival. In conclusion, protein and/or mRNA expression levels of SATB1, SMAD3, Ezrin and β-catenin may serve as potential prognostic biomarkers for PAC, both as single predictors and even better when combined. Full article

(This article belongs to the Special Issue Recent Developments and Emerging Trends in Cytoskeletal and Cell Cycle Proteins)

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17 pages, 6799 KiB

Open AccessFeature PaperArticle

Trafficking of Full-Length and N-Terminally Truncated Cathepsin B in Human Colorectal Carcinoma Cells

by Tripti Tamhane, Robin W. Njenga, Roberta E. Burden, Heiko Büth, Gunhild M. Maelandsmo, Mads H. Haugen, Christopher J. Scott and Klaudia Brix

Appl. Sci. 2021, 11(24), 11936; https://0-doi-org.brum.beds.ac.uk/10.3390/app112411936 - 15 Dec 2021

Cited by 2 | Viewed by 1473

Abstract

Cathepsin B is an endo-lysosomal cysteine protease. However, its increased expression and altered localization to the extracellular space, to mitochondria, or to the nucleus has been linked to tumor progression. In the present study, we show enhanced levels of cathepsin B in adenocarcinoma tissue in comparison to adjacent normal colon. Additionally, cathepsin B was observed in the nuclear compartment of mucosal cells in adenocarcinoma tissue samples and in the nuclei of the colorectal carcinoma cell line HCT116. Accordingly, a distinct 40-kDa form of cathepsin B was detected in HCT116 cells, which is proposed to represent a specific form lacking the signal peptide and parts of the propeptide. Trafficking studies with an EGFP-tagged N-terminally truncated form, mimicking the 40-kDa form, demonstrated accumulation in aggresome-like inclusion bodies, while EGFP-tagged full-length cathepsin B revealed regular sorting to endo-lysosomes. We conclude that the identity of nuclear cathepsin B in colorectal adenocarcinoma (in situ) and in carcinoma cells (in vitro) cannot be attributed to either full-length or 40-kDa N-terminally truncated cathepsin B forms. Hence, future studies are needed to demonstrate which form/s of cathepsin B may be sorted to the nuclei of colorectal carcinoma cells, and whether redundant regulation of related cathepsin expression occurs. Full article

(This article belongs to the Special Issue Recent Developments and Emerging Trends in Cytoskeletal and Cell Cycle Proteins)

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14 pages, 1836 KiB

Open AccessFeature PaperArticle

Anti-Genotoxicity Evaluation of Ellagic Acid and Curcumin—An In Vitro Study on Zebrafish Blood Cells

by Filomena Mottola, Renata Finelli, Concetta Iovine, Maria Carannante, Marianna Santonastaso and Lucia Rocco

Appl. Sci. 2021, 11(17), 8142; https://0-doi-org.brum.beds.ac.uk/10.3390/app11178142 - 02 Sep 2021

Cited by 5 | Viewed by 2007

Abstract

Genotoxicity is the ability of specific substances to cause DNA damage, affecting development, physiology, and reproduction. This is often mediated by induction of oxidative stress. This in vitro study aims to test the ability of two antioxidants, ellagic acid (EA, 100 µM) and curcumin (Cur, 40 µM) to protect zebrafish blood cells from the genotoxic action of benzene (10 µL/mL). Cells were treated for 30, 60, and 90 min with EA or Cur alone and in combination with benzene. The antigenotoxic role of antioxidants was evaluated in terms of cytotoxicity by trypan blue dye, genome stability by RAPD-PCR technique, DNA fragmentation and percentage of apoptotic cells using Comet and Diffusion assay, respectively. The results did not show statistical differences in terms of cell viability, genome stability, DNA damage and apoptosis between cells treated with antioxidants. When zebrafish blood cells were co-incubated with individual antioxidants and benzene, a significant improvement of these parameters was observed in comparison with cells incubated in benzene. Our results suggested that EA and Cur are able to protect zebrafish blood cells against DNA damage and apoptosis caused by mutagenic substance, and laid the foundation for future studies investigating their antigenotoxic potential in DNA oxidative damage therapy. Full article

(This article belongs to the Special Issue Recent Developments and Emerging Trends in Cytoskeletal and Cell Cycle Proteins)

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14 pages, 7255 KiB

Open AccessArticle

Chemotherapy-Induced Survivin Regulation in Acute Myeloid Leukemia Cells

by Petra Otevřelová and Barbora Brodská

Appl. Sci. 2021, 11(1), 460; https://0-doi-org.brum.beds.ac.uk/10.3390/app11010460 - 05 Jan 2021

Cited by 3 | Viewed by 2540

Abstract

Survivin is a 16.5 kDa protein highly expressed in centrosomes, where it controls proper sister chromatid separation. In addition to its function in mitosis, survivin is also involved in apoptosis. Overexpression of survivin in many cancer types makes it a suitable target for cancer therapy. Western blotting and confocal microscopy were used to characterize the effect of chemotherapy on acute myeloid leukemia (AML) cells. We found enhanced survivin expression in a panel of AML cell lines treated with cytarabine (Ara-C), which is part of a first-line induction regimen for AML therapy. Simultaneously, Ara-C caused growth arrest and depletion of the mitotic cell fraction. Subsequently, the effect of a second component of standard therapy protocol, idarubicin, and of a known survivin inhibitor, YM-155, on cell viability and survivin expression and localization in AML cells was investigated. Idarubicin reversed Ara-C-induced survivin upregulation in the majority of AML cell lines. YM-155 caused survivin deregulation together with a viability decrease in cells resistant to idarubicin treatment, suggesting that YM-155 might be efficient in a specific subset of AML patients. Expression levels of other apoptosis-related proteins, in particular X-linked inhibitor of apoptosis (XIAP), Mcl-1, and p53, and of the cell-cycle inhibitor p21 considerably changed in almost all cases, confirming the off-target effects of YM-155. Full article

(This article belongs to the Special Issue Recent Developments and Emerging Trends in Cytoskeletal and Cell Cycle Proteins)

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Review

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21 pages, 1668 KiB

Open AccessReview

The Less Known Cyclins—Uncovered

by Agnieszka Żuryń, Aleksandra Opacka, Adrian Krajewski, Wioletta Zielińska and Alina Grzanka

Appl. Sci. 2021, 11(5), 2320; https://0-doi-org.brum.beds.ac.uk/10.3390/app11052320 - 05 Mar 2021

Cited by 1 | Viewed by 1857

Abstract

Cyclins belong to a group of proteins that are cyclically produced and destructed in a cell. Cyclins are a family of proteins that are a key component of the cell cycle regulating system, which level of expression depends on the phase of the cycle. Cyclins regulate the activity of cyclin-dependent kinases (Cdk), thanks to which they influence the length of individual phases of the cell cycle and also determine whether the cell can enter the next life stage. Proper expression of cyclins plays an important role in processes such as proliferation, transcription, DNA repair and cell differentiation. However, dysregulation of their expression is one of the most important disorders leading to the development of different types of cancer, which suggests that cyclins can be defined as a prognostic marker. Currently, we may distinguish >10 members of the cyclins family participating in the division of human cells. The group of less known cyclins includes C, F, G, H, I, J, K, L, M, O, T and Y cyclins. The present report demonstrates the current state of knowledge considering less known cyclins and their role in normal and cancer cells. Full article

(This article belongs to the Special Issue Recent Developments and Emerging Trends in Cytoskeletal and Cell Cycle Proteins)

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