Cathepsin D as a Promising Target for the Discovery of Novel Anticancer Agents

Dubey, Vijaya; Luqman, Suaib

doi:10.2174/1568009616666161229145115

Cited by 35 publications

(26 citation statements)

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“…Taken together, cathepsins D and K, both extensively studied for their potential as therapeutic targets in e.g. cancer, Alzheimer or Parkinson disease 53 , 54 , may have potential as targets for novel DN treatment.…”

Section: Discussionmentioning

confidence: 99%

Urinary peptidomics analysis reveals proteases involved in diabetic nephropathy

Krochmal

Kontostathi

Magalhães

et al. 2017

Sci Rep

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Mechanisms underlying the onset and progression of nephropathy in diabetic patients are not fully elucidated. Deregulation of proteolytic systems is a known path leading to disease manifestation, therefore we hypothesized that proteases aberrantly expressed in diabetic nephropathy (DN) may be involved in the generation of DN-associated peptides in urine. We compared urinary peptide profiles of DN patients (macroalbuminuric, n = 121) to diabetic patients with no evidence of DN (normoalbuminuric, n = 118). 302 sequenced, differentially expressed peptides (adjusted p-value < 0.05) were analysed with the Proteasix tool predicting proteases potentially involved in their generation. Activity change was estimated based on the change in abundance of the investigated peptides. Predictions were correlated with transcriptomics (Nephroseq) and relevant protein expression data from the literature. This analysis yielded seventeen proteases, including multiple forms of MMPs, cathepsin D and K, kallikrein 4 and proprotein convertases. The activity of MMP-2 and MMP-9, predicted to be decreased in DN, was investigated using zymography in a DN mouse model confirming the predictions. Collectively, this proof-of-concept study links urine peptidomics to molecular changes at the tissue level, building hypotheses for further investigation in DN and providing a workflow with potential applications to other diseases.

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Section: Discussionmentioning

confidence: 99%

Urinary peptidomics analysis reveals proteases involved in diabetic nephropathy

Krochmal

Kontostathi

Magalhães

et al. 2017

Sci Rep

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“…The inhibition of CTSs has been widely explored over the last decades in the field of chronic inflammatory diseases [27,37,204,205], cardiovascular diseases [10,19,181], osteoporosis [70][71][72][73], arthritis [28,206], kidney diseases [30][31][32]84], pancreatitis [207], obesity [208][209][210], cancer [25,34,48,74,82,211], neurodegenerative diseases [39,41,184,185,212,213], and many other pathological states. Multiple inhibitors are currently available, ranging from reversible covalent inhibitors to irreversible inhibitors [214][215][216][217][218] (Table 4).…”

Section: Cathepsin Inhibitors and Their Therapeutic Applicationsmentioning

confidence: 99%

Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

Pasquale

Moles

Pavone

2020

Cells

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Cathepsins (CTSs) are ubiquitously expressed proteases normally found in the endolysosomal compartment where they mediate protein degradation and turnover. However, CTSs are also found in the cytoplasm, nucleus, and extracellular matrix where they actively participate in cell signaling, protein processing, and trafficking through the plasma and nuclear membranes and between intracellular organelles. Dysregulation in CTS expression and/or activity disrupts cellular homeostasis, thus contributing to many human diseases, including inflammatory and cardiovascular diseases, neurodegenerative disorders, diabetes, obesity, cancer, kidney dysfunction, and others. This review aimed to highlight the involvement of CTSs in inherited lysosomal storage disorders, with a primary focus to the emerging evidence on the role of CTSs in the pathophysiology of Mucopolysaccharidoses (MPSs). These latter diseases are characterized by severe neurological, skeletal and cardiovascular phenotypes, and no effective cure exists to date. The advance in the knowledge of the molecular mechanisms underlying the activity of CTSs in MPSs may open a new challenge for the development of novel therapeutic approaches for the cure of such intractable diseases.

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“…In the case of breast cancer, Derocq et al demonstrated that CATD secreted in the extracellular environment triggers fibroblast outgrowth by binding to the β-chain of the LDL receptor-related protein-1 (LRP1), a scavenger receptor mediating the endocytosis of various extracellular ligands and involved in signal transduction and gene transcription (88). The multiple roles of CATD show increasing promise for the development of novel anticancer agents (89).…”

Section: Cathepsin D and Transglutaminase 2 (Tgm2)mentioning

confidence: 99%

Biomarkers of tumor invasiveness in proteomics (Review)

et al. 2020

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Over the past two decades, quantitative proteomics has emerged as an important tool for deciphering the complex molecular events involved in cancers. The number of references involving studies on the cancer metastatic process has doubled since 2010, while the last 5 years have seen the development of novel technologies combining deep proteome coverage capabilities with quantitative consistency and accuracy. To highlight key findings within this huge amount of information, the present review identified a list of tumor invasive biomarkers based on both the literature and data collected on a biocollection of experimental cell lines, tumor models of increasing invasiveness and tumor samples from patients with colorectal or breast cancer. Crossing these different data sources led to 76 proteins of interest out of 1,245 mentioned in the literature. Information on these proteins can potentially be translated into clinical prospects, since they represent potential targets for the development and evaluation of innovative therapies, alone or in combination. Herein, a systematical review of the biology of each of these proteins, including their specific subcellular/extracellular or multiple localizations is presented. Finally, as an important advantage of quantitative proteomics is the ability to provide data on all these molecules simultaneously in cell pellets, body fluids or paraffin-embedded sections of tumors/invaded tissues, the significance of some of their interconnections is discussed.

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Cathepsin D as a Promising Target for the Discovery of Novel Anticancer Agents

Cited by 35 publications

References 0 publications

Urinary peptidomics analysis reveals proteases involved in diabetic nephropathy

Urinary peptidomics analysis reveals proteases involved in diabetic nephropathy

Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

Biomarkers of tumor invasiveness in proteomics (Review)

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