Lost or Forgotten: The nuclear cathepsin protein isoforms in cancer

Soond, Surinder M.; Kozhevnikova, M. V.; Frolova, Anastasia S.; Savvateeva, Lyudmila V.; Plotnikov, Egor Y.; Townsend, Paul A.; Han, Yuan‐Ping; Zamyatnin, Andrey A.

doi:10.1016/j.canlet.2019.07.020

Cited by 27 publications

(23 citation statements)

References 87 publications

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“…Cathepsins in the nucleus are known to process transcription factors that control cell cycle progression thus facilitating cell proliferation and differentiation (reviewed in [ 107 ]. The CDP/Cux/Cut transcription factors are a group of highly conserved proteins in higher eukaryotes that are involved in cell cycle proliferation, particularly in the transition from G1 to S phase.…”

Section: Cathepsins In Cytosolmentioning

confidence: 99%

The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management

Yadati

Houben

Bitorina

et al. 2020

Cells

238

198

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Cathepsins are the most abundant lysosomal proteases that are mainly found in acidic endo/lysosomal compartments where they play a vital role in intracellular protein degradation, energy metabolism, and immune responses among a host of other functions. The discovery that cathepsins are secreted and remain functionally active outside of the lysosome has caused a paradigm shift. Contemporary research has unraveled many versatile functions of cathepsins in extralysosomal locations including cytosol and extracellular space. Nevertheless, extracellular cathepsins are majorly upregulated in pathological states and are implicated in a wide range of diseases including cancer and cardiovascular diseases. Taking advantage of the differential expression of the cathepsins during pathological conditions, much research is focused on using cathepsins as diagnostic markers and therapeutic targets. A tailored therapeutic approach using selective cathepsin inhibitors is constantly emerging to be safe and efficient. Moreover, recent development of proteomic-based approaches for the identification of novel physiological substrates offers a major opportunity to understand the mechanism of cathepsin action. In this review, we summarize the available evidence regarding the role of cathepsins in health and disease, discuss their potential as biomarkers of disease progression, and shed light on the potential of extracellular cathepsin inhibitors as safe therapeutic tools.

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Section: Cathepsins In Cytosolmentioning

confidence: 99%

The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management

Yadati

Houben

Bitorina

et al. 2020

Cells

238

198

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“…CTSs can also be found in caveolae triggering cell-surface proteolytic events associated with cell migration [3], or in the endolysosomal [4] and autolysosomal compartments where they process the compartment's cargo [5]. CTSs in the nuclei play an important role in cell cycle regulation [6], while in the cytosol mediate mitochondrial permeabilization and apoptosis through cleavage of Bid and release of Bax [7]. Some of the cellular components displayed in the figure have been adapted from Smart Servier Medical Art under Creative Commons Attribution 3.0 Unported License.…”

mentioning

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 general, the pathway for Cathepsin proteins entering the nucleus without nuclear localization sequence (NLS) has been a controversial issue. A recent study demonstrated that Cathepsin proteins could be “chaperoned” into the nucleus from a cytoplasmic source following possible leakages from the lysosome [ 33 ]. The mechanism of Cathepsin positioning to the nucleus and its role in the nucleus are also matters for further exploration.…”

Section: Discussionmentioning

confidence: 99%

The Potential Role of Cathepsin K in Non-Small Cell Lung Cancer

et al. 2020

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(1) Background: Cathepsin K has been found overexpressed in several malignant tumors. However, there is little information regarding the involvement of Cathepsin K in non-small cell lung cancer (NSCLC). (2) Methods: Cathepsin K expression was tested in human NSCLC cell lines A549 and human embryo lung fibroblast MRC-5 cells using Western blot and immunofluorescence assay. Cathepsin K was transiently overexpressed or knocked down using transfection with a recombinant plasmid and siRNA, respectively, to test the effects on cell proliferation, migration, invasion, and on the mammalian target of rapamycin (mTOR) signaling pathway. (3) Results: Expression of Cathepsin K was increased significantly in A549 cells and diffused within the cytoplasm compared to the MRC-5 cells used as control. Cathepsin K overexpression promoted the proliferation, migration, and invasion of A549 cells, accompanied by mTOR activation. Cathepsin K knockdown reversed the above malignant behavior and inhibited the mTOR signaling activation, suggesting that Cathepsin K may promote the progression of NSCLC by activating the mTOR signaling pathway. (4) Conclusion: Cathepsin K may potentially represent a viable drug target for NSCLC treatment.

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Lost or Forgotten: The nuclear cathepsin protein isoforms in cancer

Cited by 27 publications

References 87 publications

The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management

The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management

Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

The Potential Role of Cathepsin K in Non-Small Cell Lung Cancer

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