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The Role of Lysosomal Proteases in Cancer and Infectious Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 15 July 2024 | Viewed by 1603

Special Issue Editor


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Guest Editor
Department of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of Vienna, 1090 Vienna, Austria
Interests: ion channels; cytotoxicity; lysosomal proteases

Special Issue Information

Dear Colleagues,

Lysosomal proteases are classified into three classes according to their active sites, cysteine cathepsins (which include cathepsins B, H, V, W, K, L, X, C, S, F and O), serine cathepsins (which include cathepsins G and A), and aspartic cathepsins (which include their two members cathepsins D and E). Most lysosomal proteases are involved in a wide range of physiological processes like the breakdown of intracellular proteins, energy metabolism and immune responses among many other functions. Lysosomal proteases are also implicated in different diseases including cancer metastasis, neurodegenerative diseases, and inflammation.

The aim of this Special Issue is to develop the knowledge of lysosomal proteases and explore how they play an important role in physiological processes and diseases. Authors are invited to submit original research and review articles that address these topics.

Topics of interest include, but are not limited to, the following:

  • Impact of lysosomal proteases in cancer;
  • Impact of lysosomal proteases in viral diseases;
  • Impact of lysosomal proteases in neurodegenerative diseases and inflammation;
  • Effect of lysosomal protease inhibitors on tumor progression;
  • Effect of lysosomal proteases on radiation therapy treatment;
  • Induction of apoptosis of lysosomal cathepsin inhibitors in cancer cells;
  • Molecular mechanism underlying the inhibition of lysosomal proteases;
  • Role of lysosomal proteases on the cytotoxicity of fungal and bacterial toxins;
  • Role of lysosomal proteases in aging.

Prof. Dr. Christian Studenik
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cathepsins
  • lysosomes
  • apoptosis
  • autophagy
  • cancer
  • cell cycle
  • metastasis
  • molecular tumor pathology
  • radiation therapy
  • therapeutic targets
  • translational cancer research
  • treatment response
  • tumor microenvironment
  • viral infections

Published Papers (1 paper)

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Research

15 pages, 2814 KiB  
Article
The Significance of Cathepsin B in Mediating Radiation Resistance in Colon Carcinoma Cell Line (Caco-2)
by Ramadan F. Abdelaziz, Ahmed M. Hussein, Mohamed H. Kotob, Christina Weiss, Krzysztof Chelminski, Christian R. Studenik and Mohammed Aufy
Int. J. Mol. Sci. 2023, 24(22), 16146; https://doi.org/10.3390/ijms242216146 - 09 Nov 2023
Cited by 3 | Viewed by 1364
Abstract
Cathepsins (Caths) are lysosomal proteases that participate in various physiological and pathological processes. Accumulating evidence suggests that caths play a multifaceted role in cancer progression and radiotherapy resistance responses. Their proteolytic activity influences the tumor’s response to radiation by affecting oxygenation, nutrient availability, [...] Read more.
Cathepsins (Caths) are lysosomal proteases that participate in various physiological and pathological processes. Accumulating evidence suggests that caths play a multifaceted role in cancer progression and radiotherapy resistance responses. Their proteolytic activity influences the tumor’s response to radiation by affecting oxygenation, nutrient availability, and immune cell infiltration within the tumor microenvironment. Cathepsin-mediated DNA repair mechanisms can promote radioresistance in cancer cells, limiting the efficacy of radiotherapy. Additionally, caths have been associated with the activation of prosurvival signaling pathways, such as PI3K/Akt and NF-κB, which can confer resistance to radiation-induced cell death. However, the effectiveness of radiotherapy can be limited by intrinsic or acquired resistance mechanisms in cancer cells. In this study, the regulation and expression of cathepsin B (cath B) in the colon carcinoma cell line (caco-2) before and after exposure to radiation were investigated. Cells were exposed to escalating ionizing radiation doses (2 Gy, 4 Gy, 6 Gy, 8 Gy, and 10 Gy). Analysis of protein expression, in vitro labeling using activity-based probes DCG04, and cath B pull-down revealed a radiation-induced up-regulation of cathepsin B in a dose-independent manner. Proteolytic inhibition of cathepsin B by cathepsin B specific inhibitor CA074 has increased the cytotoxic effect and cell death due to ionizing irradiation treatment in caco-2 cells. Similar results were also obtained after cathepsin B knockout by CRISPR CAS9. Furthermore, upon exposure to radiation treatment, the inhibition of cath B led to a significant upregulation in the expression of the proapoptotic protein BAX, while it induced a significant reduction in the expression of the antiapoptotic protein BCL-2. These results showed that cathepsin B could contribute to ionizing radiation resistance, and the abolishment of cathepsin B, either by inhibition of its proteolytic activity or expression, has increased the caco-2 cells susceptibility to ionizing irradiation. Full article
(This article belongs to the Special Issue The Role of Lysosomal Proteases in Cancer and Infectious Diseases)
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