Unconventional Secretion of Heat Shock Proteins in Cancer

Santos, Tiago G.; Martins, Vilma R.; Hajj, Glaucia Noeli Maroso

doi:10.3390/ijms18050946

Cited by 60 publications

(41 citation statements)

References 171 publications

(182 reference statements)

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“…Similarly, we detected higher abundance of chaperone proteins such as endoplasmin (HSP90B1), heat shock protein family H (Hsp110) member 1 (HSPH1) which have been reported in several cancers previously [66]. In addition, we also detected decreased abundance of ECM proteins such as matrix metallopeptidase 9 (MMP9), secreted protein acidic and rich in cysteine (SPARC) and cysteine rich angiogenic inducer 61 (CYR61) among others in OKF6/TERT1-Shisha secretome.…”

Section: Discussionsupporting

confidence: 76%

Secretome analysis of oral keratinocytes chronically exposed to shisha

Patil

Babu

Subbannayya

et al. 2019

CBM

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BACKGROUND: Shisha smoking has been associated with multiple diseases including oral cancer. However, a mechanistic study to investigate alteration of secreted proteins in oral cells due to shisha smoking is lacking. OBJECTIVES: Elucidation of differentially secreted proteins by immortalized human normal oral keratinocytes (OKF6/TERT1) upon chronic exposure to shisha. METHODS: OKF6/TERT1 was chronically treated with 0.5% shisha extract for 8 months. Conditioned media from shisha treated (OKF6/TERT1-Shisha) and untreated (OKF6/TERT1-Parental) cells were subjected to TMT-based quantitative proteomic analysis. Bioinformatics analysis of differentially secreted proteins was carried out using SignalP, SecretomeP and TMHMM. Immunoblot validation of selected proteins was carried out to confirm the proteomics results. RESULTS: Proteomic analysis of OKF6/TERT1-Parental and OKF6/TERT1-Shisha secretome resulted in the identification of 1,598 proteins, of which 218 proteins were found to be differentially secreted (≥ 1.5-fold; p-value ≤ 0.05) in shisha treated cells. Bioinformatics analysis using prediction tools showed secretory potential of differentially secreted proteins identified in OKF6/TERT1-Shisha. Western blotting validated the expression of AKR1C2, HSPH1 and MMP9 in OKF6/TERT1-Shisha secretome in agreement with proteomic data. CONCLUSION: This study serves as a useful resource to understand the effect of chronic shisha smoking on the milieu of secreted proteins of oral cells. In vivo studies are warranted to supplement our in vitro data to elucidate the role of these proteins as early diagnostic biomarkers for oral carcinogenesis among shisha smokers.

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Section: Discussionsupporting

confidence: 76%

Secretome analysis of oral keratinocytes chronically exposed to shisha

Patil

Babu

Subbannayya

et al. 2019

CBM

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“…There was no significant difference between HSP 60 levels in placebo group and vitamin D group before and after intervention. Oxidative stress, infection, heat, and immune diseases may stimulate body production of HSP 60, and conclusively increase inflammatory complications [ 26 ]. Various studies have suggested that vitamin D may reduce oxidative stress [ 27 ], which decreases HSP 60 production.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D supplementation and serum heat shock protein 60 levels in patients with coronary heart disease: a randomized clinical trial

et al. 2018

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BackgroundThe aim in this study was to investigate the effect of vitamin D (25(OH)D3) supplementation on heat shock protein 60 (HSP 60) and other inflammatory markers (IL-17, TNF-α, PAB) in patients with coronary heart disease (CHD).MethodsIn this double-blind, randomized clinical trial, we recruited 80 male and female patients aged 30–60 with CHD and 25(OH)D3 serum levels < 30 ng/ml from Rasool-e-Akram Hospital in Tehran, Iran. Serum levels of HSP 60 as primary outcome, and 25(OH)D3, IL-17, TNF-α, PAB, lipid profiles and parathyroid hormone (PTH) as secondary outcomes were measured at baseline and post-intervention. We randomly assigned eligible participants to a placebo group (N = 40) or an intervention group (N = 40) (50,000 IU/wk. vitamin D supplement) for eight weeks.ResultsThe results demonstrated that vitamin D supplementation resulted in a significant increase in 25(OH) D3 serum levels in the intervention group compared to the placebo group (46.86 vs. 7.28 ng/ml). PTH levels decreased in the intervention group compared to the placebo group (− 19.81 vs. 2.92 pg/ml) after eight weeks of supplementation. Furthermore, we observed a significant change in waist circumference (− 0.97 vs. -0.26 cm), fat percentage (−.13 vs. 0.1%), systolic blood pressure (− 3.85 vs. -2.11 mmHg) and diastolic blood presure (− 4 vs. -1.86 mmHg) in the vitamin D group compared to the placebo group (all P values < 0.05). Other variables did not significantly change after the intervention.ConclusionBased on our findings, weekly vitamin D supplementation of 50,000 IU for eight weeks in patients with CHD resulted in decreased systolic and diastolic blood pressure, waist circumference and fat percentage. No significant effect on HSP 60, inflammatory markers or lipid profiles was observed.Trial registrationIRCT, IRCT201612122365N14. Registered 12 December 2016.

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“…Recent developments in the field have contributed to significant advances in the understanding of the molecular processes involved in UPS (Daniels and Brough, 2017;Pompa et al, 2017;Ponpuak et al, 2015;Rabouille, 2017;Santos et al, 2017). Nevertheless, a comprehensive description that adequately explains the role in UPS in disease pathogenesis is currently lacking.…”

Section: Introductionmentioning

confidence: 99%

Unconventional protein secretion – new insights into the pathogenesis and therapeutic targets of human diseases

Kim

Gee

Lee

2018

Journal of Cell Science

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Most secretory proteins travel through a well-documented conventional secretion pathway involving the endoplasmic reticulum (ER) and the Golgi complex. However, recently, it has been shown that a significant number of proteins reach the plasma membrane or extracellular space via unconventional routes. Unconventional protein secretion (UPS) can be divided into two types: (i) the extracellular secretion of cytosolic proteins that do not bear a signal peptide (i.e. leaderless proteins) and (ii) the cell-surface trafficking of signal-peptide-containing transmembrane proteins via a route that bypasses the Golgi. Understanding the UPS pathways is not only important for elucidating the mechanisms of intracellular trafficking pathways but also has important ramifications for human health, because many of the proteins that are unconventionally secreted by mammalian cells and microorganisms are associated with human diseases, ranging from common inflammatory diseases to the lethal genetic disease of cystic fibrosis. Therefore, it is timely and appropriate to summarize and analyze the mechanisms of UPS involvement in disease pathogenesis, as they may be of use for the development of new therapeutic approaches. In this Review, we discuss the intracellular trafficking pathways of UPS cargos, particularly those related to human diseases. We also outline the disease mechanisms and the therapeutic potentials of new strategies for treating UPS-associated diseases.

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Unconventional Secretion of Heat Shock Proteins in Cancer

Cited by 60 publications

References 171 publications

Secretome analysis of oral keratinocytes chronically exposed to shisha

Secretome analysis of oral keratinocytes chronically exposed to shisha

Vitamin D supplementation and serum heat shock protein 60 levels in patients with coronary heart disease: a randomized clinical trial

Unconventional protein secretion – new insights into the pathogenesis and therapeutic targets of human diseases

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