Kallistatin suppresses cancer development by multi-factorial actions

Chao, Julie; Li, Pengfei; Chao, Lee

doi:10.1016/j.critrevonc.2017.03.011

Cited by 20 publications

(19 citation statements)

References 102 publications

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“…Kallistatin's active site is essential for inhibiting tissue kallikrein's activity and modulating the synthesis of microRNAs, (miR-34a, miR-21 and miR-203) among other functions. Also, kallistatin's heparin-binding site is crucial for antagonizing the signalling pathways of vascular endothelial growth factor, tumour necrosis factor-α, wnt, transforming growth factor-β and epidermal growth factor (86). Another protein family detected in CM-T3 was SLC transporters (SLC2A1, SLC2A14, SLC4A1 and SLC9A3R).…”

Section: Bar Charts Of Exclusive Enriched Biological Pathways For Cmentioning

confidence: 99%

Human Periprostatic Adipose Tissue: Secretome from Patients With Prostate Cancer or Benign Prostate Hyperplasia

Sacca

Mazza

Scorticati

et al. 2018

Cancer Genomics Proteomics

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Background/Aim: Periprostatic adipose tissue (PPAT) directs tumour behaviour. Microenvironment secretome provides information related to its biology. This study was performed to identify secreted proteins by PPAT, from both prostate cancer and benign prostate hyperplasia (BPH) patients. Patients and Methods: Liquid chromatography-mass spectrometry-based proteomic analysis was performed in PPAT-conditioned media (CM) from patients with prostate cancer (CMs-T) (stage T3: CM-T3, stage T2: CM-T2) or benign disease (CM-BPH). Results: The highest number and diversity of proteins was identified in CM-T3. Locomotion was the biological process mainly associated to CMs-T and reproduction to CM-T3. Immune responses were enriched in CMs-T. Extracellular matrix and structural proteins were associated to CMs-T. CM-T3 was enriched in proteins with catalytic activity and CM-T2 in proteins with defense/immunity activity. Metabolism and energy pathways were enriched in CM-T3 and those with immune system functions in CMs-T. Transport proteins were enriched in CM-T2 and CM-BPH. Conclusion: Proteins and pathways reported in this study could be useful to distinguish stages of disease and may become targets for novel therapies.

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Section: Bar Charts Of Exclusive Enriched Biological Pathways For Cmentioning

confidence: 99%

Human Periprostatic Adipose Tissue: Secretome from Patients With Prostate Cancer or Benign Prostate Hyperplasia

Sacca

Mazza

Scorticati

et al. 2018

Cancer Genomics Proteomics

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“…Hyperbaric oxygen therapy has been shown to prolong survival of mice with systemic metastatic cancer, reduces the growth, and induces apoptosis in rat mammary tumors [ 43 ]. Indeed, our previous study showed that hyperoxia markedly induces kallistatin expression in MDA-MB-231 and MCF-7 breast cancer cells and kallistatin treatment inhibits tumor progression by inducing cancer cell apoptosis and autophagy [ 11 , 28 ]. Therefore, mild oxygen or hyperbaric oxygen upregulates kallistatin, HIF-1, and eNOS expression and thus NO formation.…”

Section: Mild Oxygen or Hyperoxia Upregulates Kallistatin Hif-1 mentioning

confidence: 99%

“…Oxidative stress downregulates kallistatin expression by activating c-Jun NH 2 -terminal kinase- (JNK-) dependent FOXO1 signaling in cultured endothelial cells [ 27 ]. However, hyperoxia treatment markedly stimulates kallistatin expression in breast cancer cells [ 28 ]. Moreover, kallistatin exhibits antioxidative actions.…”

Section: Introductionmentioning

confidence: 99%

“…Kallistatin via its heparin-binding site antagonizes cytokine-induced reactive oxygen species (ROS) formation, and its active site is responsible for the upregulation of antioxidant gene expression in endothelial cells [ 9 , 10 , 29 ]. On the other hand, kallistatin stimulates ROS formation in immune cells, leading to marked bacterial killing activity in septic mice [ 28 , 30 ]. Moreover, kallistatin's vasodilating activity is partly mediated by H 2 O 2 formation [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, kallistatin stimulates ROS formation in immune cells, leading to marked bacterial killing activity in septic mice [ 28 , 30 ]. Moreover, kallistatin's vasodilating activity is partly mediated by H 2 O 2 formation [ 28 ]. Therefore, oxidative stress plays opposite roles in the regulation of kallistatin synthesis, and kallistatin possesses a dual role in modulating oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

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Opposing Effects of Oxygen Regulation on Kallistatin Expression: Kallistatin as a Novel Mediator of Oxygen-Induced HIF-1-eNOS-NO Pathway

Chao

Guo

et al. 2017

Oxidative Medicine and Cellular Longevity

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Oxidative stress has both detrimental and beneficial effects. Kallistatin, a key component of circulation, protects against vascular and organ injury. Serum kallistatin levels are reduced in patients and animal models with hypertension, diabetes, obesity, and cancer. Reduction of kallistatin levels is inversely associated with elevated thiobarbituric acid-reactive substance. Kallistatin therapy attenuates oxidative stress and increases endothelial nitric oxide synthase (eNOS) and NO levels in animal models. However, kallistatin administration increases reactive oxygen species formation in immune cells and bacterial killing activity in septic mice. High oxygen inhibits kallistatin expression via activating the JNK-FOXO1 pathway in endothelial cells. Conversely, mild oxygen/hyperoxia stimulates kallistatin, eNOS, and hypoxia-inducible factor-1 (HIF-1) expression in endothelial cells and in the kidney of normal mice. Likewise, kallistatin stimulates eNOS and HIF-1, and kallistatin antisense RNA abolishes oxygen-induced eNOS and HIF-1 expression, indicating a role of kallistatin in mediating mild oxygen's stimulation on antioxidant genes. Protein kinase C (PKC) activation mediates HIF-1-induced eNOS synthesis in response to hyperoxia/exercise; thus, mild oxygen through PKC activation stimulates kallistatin-mediated HIF-1 and eNOS synthesis. In summary, oxidative stress induces down- or upregulation of kallistatin expression, depending on oxygen concentration, and kallistatin plays a novel role in mediating oxygen/exercise-induced HIF-1-eNOS-NO pathway.

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Protective role of kallistatin in renal fibrosis via modulation of Wnt/β-catenin signaling

Yiu

Lok

et al. 2021

Clinical Science

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Kallistatin is a multiple functional serine protease inhibitor that protects against vascular injury, organ damage and tumor progression. Kallistatin treatment reduces inflammation and fibrosis in the progression of chronic kidney disease (CKD), but the molecular mechanisms underlying this protective process and whether kallistatin plays an endogenous role are incompletely understood. In the present study, we observed that renal kallistatin levels were significantly lower in patients with CKD. It was also positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with serum creatinine level. Unilateral ureteral obstruction (UUO) in animals also led to down-regulation of kallistatin protein in the kidney, and depletion of endogenous kallistatin by antibody injection resulted in aggravated renal fibrosis, which was accompanied by enhanced Wnt/β-catenin activation. Conversely, overexpression of kallistatin attenuated renal inflammation, interstitial fibroblast activation and tubular injury in UUO mice. The protective effect of kallistatin was due to the suppression of TGF-β and β-catenin signaling pathways and subsequent inhibition of epithelial-to-mesenchymal transition (EMT) in cultured tubular cells. In addition, kallistatin could inhibit TGF-β-mediated fibroblast activation via modulation of Wnt4/β-catenin signaling pathway. Therefore, endogenous kallistatin protects against renal fibrosis by modulating Wnt/β-catenin-mediated EMT and fibroblast activation. Down-regulation of kallistatin in the progression of renal fibrosis underlies its potential as a valuable clinical biomarker and therapeutic target in CKD.

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Kallistatin suppresses cancer development by multi-factorial actions

Cited by 20 publications

References 102 publications

Human Periprostatic Adipose Tissue: Secretome from Patients With Prostate Cancer or Benign Prostate Hyperplasia

Human Periprostatic Adipose Tissue: Secretome from Patients With Prostate Cancer or Benign Prostate Hyperplasia

Opposing Effects of Oxygen Regulation on Kallistatin Expression: Kallistatin as a Novel Mediator of Oxygen-Induced HIF-1-eNOS-NO Pathway

Protective role of kallistatin in renal fibrosis via modulation of Wnt/β-catenin signaling

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