Leading the invasion: The role of Cathepsin S in the tumour microenvironment

McDowell, Sara H.; Gallaher, Samantha A.; Burden, Roberta E.; Scott, Christopher J.

doi:10.1016/j.bbamcr.2020.118781

Cited by 30 publications

(28 citation statements)

References 115 publications

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“…The expression and activity of these cathepsins is generally upregulated in (chronic) inflammation and in cancers. Consequently, they are overexpressed in tumors, prominently for CatB and CatS, including in follicular lymphoma, gastric, colon, brain, breast, and pancreatic cancer [1,3,6]. Overall, most but not all of these cathepsin-mediated mechanisms result in enhanced ECM turnover and angiogenesis, clearing the way for tumor expansion, securing the cancers' nutrient supply, and, most notably, in suppressing the T-cell induced anti-cancer immune response that is located in the TME.…”

Section: Cysteine Cathepsins In Tumor Progressionmentioning

confidence: 99%

Novel Opportunities for Cathepsin S Inhibitors in Cancer Immunotherapy by Nanocarrier-Mediated Delivery

Fuchs

Novel Opportunities for Cathepsin S Inhibitors in Cancer Immunotherapy by Nanocarrier-Mediated Delivery

Fuchs

Association of Circulating Cathepsin S and Cardiovascular Disease Among Patients With Type 2 Diabetes: A Cross-Sectional Community-Based Study

Shi

Lü

et al. 2021

Front. Endocrinol.

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BackgroundCathepsin S, as an adipokine, was reported to play a critical role in various disease, including atherosclerosis and diabetes. The present study aims to elucidate the relationship between circulating cathepsin S and cardiovascular disease (CVD) in patients with type 2 diabetes.MethodsA total of 339 type 2 diabetes individuals were enrolled in this cross-sectional community-based study. Basic information, medical and laboratory data were collected. Serum cathepsin S levels were assessed by ELISA.ResultsCompared to the CVD (−) group, levels of serum cathepsin S were significantly higher in the CVD (+) group, with the median 23.68 ng/ml (18.54–28.02) and 26.81 ng/ml (21.19–37.69) respectively (P < 0.001). Moreover, patients with acute coronary syndrome (ACS) had substantially higher levels of serum cathepsin S than those with stable angina pectoris (SAP), with the median 34.65 ng/ml (24.33–42.83) and 25.52 ng/ml (20.53–31.47) respectively (P < 0.01). The spearman correlation analysis showed that circulating cathepsin S was correlated with several cardiovascular risk factors. The univariate and multivariate logistic regression analysis revealed that circulating cathepsin S was an independent risk factor for CVD (all P < 0.001) after adjustment for potential confounders. Restricted cubic spline analysis showed circulating cathepsin S had a linearity association with CVD. In addition, receiver operating characteristic (ROC) curve analysis demonstrated that the area under curve (AUC) values of cathepsin S was 0.80 (95% CI: 0.75–0.84, P < 0.001), with the optimal cutoff value of cathepsin 26.28 ng/ml.ConclusionCirculating cathepsin S was significantly higher in the CVD (+) group than that in the CVD (−) one among type 2 diabetes. The increased serum cathepsin S levels were associated with increased risks of CVD, even after adjusting for potential confounders. Thus, cathepsin S might be a potential diagnostic biomarker for CVD.

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“…It highlighted the potential of the α-ketoamide-based highly selective cathepsin S inhibitor RJW-58 in the suppression of cervical cancer cell migration and invasion of cervical cancer cells [ 204 ]. Cathepsin S, a lysosomal cysteine protease, has been reported to be associated with the degradation of the extracellular matrix, thus promoting cell migration and invasion [ 205 ]. Results of immunoprecipitation assays demonstrated that cathepsin S interacted with STIM1, which was reversed by RNAi-mediated silencing and enzymatic inhibition of cathepsin S. Analyses of confocal microscopic and super-resolution imaging indicated that cathepsin S inhibition led to STIM1 puncta accumulation in the ER and interrupted the STIM1-EB1 interaction, a critical step for STIM1 trafficking towards the cell periphery.…”

Section: Intracellular Ca 2+ Homeostasis and Store-operated Ca 2+ Entry (Soce)mentioning

confidence: 99%

The Important Role of Ion Transport System in Cervical Cancer

Chen

Shen

2021

IJMS

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Cervical cancer is a significant gynecological cancer and causes cancer-related deaths worldwide. Human papillomavirus (HPV) is implicated in the etiology of cervical malignancy. However, much evidence indicates that HPV infection is a necessary but not sufficient cause in cervical carcinogenesis. Therefore, the cellular pathophysiology of cervical cancer is worthy of study. This review summarizes the recent findings concerning the ion transport processes involved in cell volume regulation and intracellular Ca2+ homeostasis of epithelial cells and how these transport systems are themselves regulated by the tumor microenvironment. For cell volume regulation, we focused on the volume-sensitive Cl− channels and K+-Cl− cotransporter (KCC) family, important regulators for ionic and osmotic homeostasis of epithelial cells. Regarding intracellular Ca2+ homeostasis, the Ca2+ store sensor STIM molecules and plasma membrane Ca2+ channel Orai proteins, the predominant Ca2+ entry mechanism in epithelial cells, are discussed. Furthermore, we evaluate the potential of these membrane ion transport systems as diagnostic biomarkers and pharmacological interventions and highlight the challenges.

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Leading the invasion: The role of Cathepsin S in the tumour microenvironment

Cited by 30 publications

References 115 publications

Novel Opportunities for Cathepsin S Inhibitors in Cancer Immunotherapy by Nanocarrier-Mediated Delivery

Novel Opportunities for Cathepsin S Inhibitors in Cancer Immunotherapy by Nanocarrier-Mediated Delivery

Association of Circulating Cathepsin S and Cardiovascular Disease Among Patients With Type 2 Diabetes: A Cross-Sectional Community-Based Study

The Important Role of Ion Transport System in Cervical Cancer

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