Stress-resistant Translation of Cathepsin L mRNA in Breast Cancer Progression

Tholen, Martina; Wolanski, Julia; Stolze, B.; Chiabudini, Marco; Gajda, Mieczysław; Bronsert, Peter; Stickeler, Elmar; Rospert, Sabine; Reinheckel, Thomas

doi:10.1074/jbc.m114.624353

Cited by 22 publications

(19 citation statements)

References 44 publications

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“…Otherwise, it was not possible to find any correlation between the known activity of the remaining six genes found up-regulated by PRSE (Ccl7, Ctsl, Cxcr4, Itgb3, Mmp19, Mmp3) since their functions are generally associated to the acquisition of invasive features 44 48 49 50 51 .…”

Section: Discussionmentioning

confidence: 97%

Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells

Amatori

Mazzoni

Álvarez-Suarez

et al. 2016

Sci Rep

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We describe the biological effects of a polyphenol-rich strawberry extract (PRSE), obtained from the “Alba” variety, on the highly aggressive and invasive basal-like breast cancer cell line A17. Dose-response and time-course experiments showed that PRSE is able to decrease the cellular viability of A17 cells in a time- and dose-dependent manner. PRSE effect on cell survival was investigated in other tumor and normal cell lines of both mouse and human origin, demonstrating that PRSE is more active against breast cancer cells. Cytofluorimetric analysis of A17 cells demonstrated that sub-lethal doses of PRSE reduce the number of cells in S phase, inducing the accumulation of cells in G1 phase of cell cycle. In addition, the migration of A17 cells was studied monitoring the ability of PRSE to inhibit cellular mobility. Gene expression analysis revealed the modulation of 12 genes playing different roles in the cellular migration, adhesion and invasion processes. Finally, in vivo experiments showed the growth inhibition of A17 cells orthotopically transplanted into FVB syngeneic mice fed with PRSE. Overall, we demonstrated that PRSE exerts important biological activities against a highly invasive breast cancer cell line both in vitro and in vivo suggesting the strawberry extracts as preventive/curative food strategy.

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Section: Discussionmentioning

confidence: 97%

Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells

Amatori

Mazzoni

Álvarez-Suarez

et al. 2016

Sci Rep

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“…To mimic ischemia, cell were grown to 70 % confluency, washed three times with PBS and incubated in DMEM serum free supplied with SAR1 or DMSO for 24 h in a special incubation bag containing Anaerocult ® A mini (Merck, Darmstadt, Germany), a chemical mixture that completely binds oxygen, creating an oxygen-free environment. The bag was sealed and severe hypoxia (<0.5 % O 2 ) was assessed by color change of a test strip (Anaerotest, Merck) from blue to white within the first 90 min of incubation [ 16 , 17 ]. Human umbilical vein endothelial cells (HUVECs) were kindly provided by Dr. Jennifer Esser.…”

Section: Methodsmentioning

confidence: 99%

Cathepsin A inhibition attenuates myocardial infarction-induced heart failure on the functional and proteomic levels

et al. 2016

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BackgroundMyocardial infarction (MI) is a major cause of heart failure. The carboxypeptidase cathepsin A is a novel target in the treatment of cardiac failure. We aim to show that recently developed inhibitors of the protease cathepsin A attenuate post-MI heart failure.MethodsMice were subjected to permanent left anterior descending artery (LAD) ligation or sham operation. 24 h post–surgery, LAD-ligated animals were treated with daily doses of the cathepsin A inhibitor SAR1 or placebo. After 4 weeks, the three groups (sham, MI-placebo, MI-SAR1) were evaluated.ResultsCompared to sham-operated animals, placebo-treated mice showed significantly impaired cardiac function and increased plasma BNP levels. Cathepsin A inhibition prevented the increase of plasma BNP levels and displayed a trend towards improved cardiac functionality. Proteomic profiling was performed for the three groups (sham, MI-placebo, MI-SAR1). More than 100 proteins were significantly altered in placebo-treated LAD ligation compared to the sham operation, including known markers of cardiac failure as well as extracellular/matricellular proteins. This ensemble constitutes a proteome fingerprint of myocardial infarction induced by LAD ligation in mice. Cathepsin A inhibitor treatment normalized the marked increase of the muscle stress marker CA3 as well as of Igγ 2b and fatty acid synthase. For numerous further proteins, cathepsin A inhibition partially dampened the LAD ligation-induced proteome alterations.ConclusionsOur proteomic and functional data suggest that cathepsin A inhibition has cardioprotective properties and support a beneficial effect of cathepsin A inhibition in the treatment of heart failure after myocardial infarction.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0907-8) contains supplementary material, which is available to authorized users.

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“…Examples are their role in immunity and infection , processing of peptide hormones , termination of growth factor signaling , and copper homeostasis . Dysregulated cathepsins have also been found to have key roles in various disease entities such as cancers , kidney diseases , and autoimmune diseases . Consequently, cathepsins are also under investigation as drug targets.…”

Section: Introductionmentioning

confidence: 99%

Inherited diseases caused by mutations in cathepsin protease genes

et al. 2017

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Lysosomal cathepsins are proteolytic enzymes increasingly recognized as prognostic markers and potential therapeutic targets in a variety of diseases. In those conditions, the cathepsins are mostly overexpressed, thereby driving the respective pathogenic processes. Although less known, there are also diseases with a genetic deficiency of cathepsins. In fact, nowadays 6 of the 15 human proteases called ‘cathepsins’ have been linked to inherited syndromes. However, only three of these syndromes are typical lysosomal storage diseases, while the others are apparently caused by defective cleavage of specific protein substrates. Here, we will provide an introduction on lysosomal cathepsins, followed by a brief description of the clinical symptoms of the various genetic diseases. For each disease, we focus on the known mutations of which many have been only recently identified by modern genome sequencing approaches. We further discuss the effect of the respective mutation on protease structure and activity, the resulting pathogenesis, and possible therapeutic strategies.

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Stress-resistant Translation of Cathepsin L mRNA in Breast Cancer Progression

Cited by 22 publications

References 44 publications

Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells

Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells

Cathepsin A inhibition attenuates myocardial infarction-induced heart failure on the functional and proteomic levels

Inherited diseases caused by mutations in cathepsin protease genes

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