Role of Serine Proteases and Inhibitors in Cancer

Poddar, Nitesh Kumar; Maurya, Sanjeev Kumar; Saxena, Vanshika

doi:10.1007/978-981-10-2513-6_12

Cited by 11 publications

(7 citation statements)

References 148 publications

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“…The serine-type endopeptidase activity was found to be associated with the progression of OSCC. The dysregulation of serine-type endopeptidase activity may lead to degradation of the extracellular matrix and imbalance of cellular homeostasis in cancers ( Poddar, Maurya & Saxena, 2017 ). Additionally, other functional processes such as binding, catalytic, and transportation are known to be associated with carcinogenesis ( Basten & Giles, 2013 ; Oruganty et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Comparative sera proteomics analysis of differentially expressed proteins in oral squamous cell carcinoma

Wong

Ramanathan

Yuen

et al. 2021

PeerJ

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Background Oral squamous cell carcinoma (OSCC) has increased in incidence from 1990 to 2017, especially in South and Southeast Asia. It is often diagnosed at an advanced stage with a poor prognosis. Therefore, early detection of OSCC is essential to improve the prognosis of OSCC. This study aims to identify the differentially expressed serum proteins as potential biomarkers for oral squamous cell carcinoma (OSCC). Methods Comparative proteomics profiling of serum samples from OSCC patients, oral potentially malignant disorder (OPMD) patients, and healthy individuals were performed using two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry (MS) (n = 60) and bioinformatics analysis. The enzyme-linked immunosorbent assay (ELISA) (n = 120) and immunohistochemistry (IHC) (n = 70) were used to confirm our findings. Results The 2-DE analysis revealed that 20 differentially expressed proteins were detected in OPMD and OSCC (p < 0.05). Bioinformatics analysis indicated that the activation of classical complement, liver X receptor/retinoid X receptor (LXR/RXR) activation, and acute phase response signaling pathway are associated with the development and progression of OSCC. Most of the detected proteins are acute-phase proteins and were related to inflammation and immune responses, including apolipoprotein A-I (APOA1), complement C3 (C3), clusterin (CLU), and haptoglobin (HP). The expression levels of CLU and HP in ELISA are consistent with the findings from the 2-DE analysis, except for the mean serum level of HP in OPMD, whereby it was slightly higher than that in control. IHC results demonstrated that CLU and HP are significantly decreased in OSCC tissues. Conclusion Decreased expression of CLU and HP could serve as complementary biomarkers of OSCC. These proteins may assist in predicting the outcomes of OSCC patients. However, a larger cohort is needed for further investigation.

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Section: Discussionmentioning

confidence: 99%

Comparative sera proteomics analysis of differentially expressed proteins in oral squamous cell carcinoma

Wong

Ramanathan

Yuen

et al. 2021

PeerJ

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“…Serine proteases (SPs) have been reported to be abnormally regulated in diverse chronic diseases 14,[56][57][58] . For example, during carcinogenic development SPs influence metastasis and cancer progression 59,60 , while in the context of diabetes they control fibrinolysis, coagulation and inflammation which in turn affects disease severity 57 .…”

Section: Discussionmentioning

confidence: 99%

SPINT2 controls SARS-CoV-2 viral infection and is associated to disease severity

Alvarez

Sharma

Kee

et al. 2020

Preprint

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COVID-19 outbreak is the biggest threat to human health in recent history. Currently, there are over 1.5 million related deaths and 75 million people infected around the world (as of 22/12/2020). The identification of virulence factors which determine disease susceptibility and severity in different cell types remains an essential challenge. The serine protease TMPRSS2 has been shown to be important for S protein priming and viral entry, however, little is known about its regulation. SPINT2 is a member of the family of Kunitz type serine protease inhibitors and has been shown to inhibit TMPRSS2. Here, we explored the existence of a co-regulation between SPINT2/TMPRSS2 and found a tightly regulated protease/inhibitor expression balance across tissues. We found that SPINT2 negatively correlates with SARS-CoV-2 expression in Calu-3 and Caco-2 cell lines and was down-regulated in secretory cells from COVID-19 patients. We validated our findings using Calu-3 cell lines and observed a strong increase in viral load after SPINT2 knockdown. Additionally, we evaluated the expression of SPINT2 in datasets from comorbid diseases using bulk and scRNA-seq data. We observed its down-regulation in colon, kidney and liver tumors as well as in alpha pancreatic islets cells from diabetes Type 2 patients, which could have implications for the observed comorbidities in COVID-19 patients suffering from chronic diseases.

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“…PRSS family members showed highly various functions modulating immunity, carcinogenesis, and cancer progression. 26,27 The members in this family have been reported to show pro-tumor effects in prostate cancer, 28 diffuse large B-cell lymphoma, 27 pancreatic cancer, 29 colorectal cancer 30 and gastric cancer. 31 Considering there was no other studies reporting their function in glioma to the best of our knowledge, we tried to study the effect of PRSS family in glioma via bioinformatic tools.…”

Section: High Htra1 Expression Is Correlated With Increasing Grade Of...mentioning

confidence: 99%

HTRA1 promotes EMT through the HDAC6/Ac‐α‐tubulin pathway in human GBM cells

Zhao,

Wu,

Wang

et al. 2024

CNS Neurosci Ther

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BackgroundThe infiltrative nature of human gliomas renders complete surgical removal of tumors futile. Thus, illuminating mechanisms of their infiltrative properties may improve therapies and outcomes of glioma patients.MethodsComprehensive bioinformatic analyses of PRSS family were undertaken. Transfection of HTRA1 siRNAs was used to suppress HTRA1 expression. CCK‐8, EdU, and colony formation assay were employed to assess cell viability, and cell migration/invasion was detected by transwell, wound healing, and 3D tumor spheroid invasion assays. Immunoprecipitation was applied to study the mechanism that HTRA1 affected cell migration. In addition, in situ xenograft tumor model was employed to explore the role of HTRA1 in glioma growth in vivo.ResultsHTRA1 knockdown could lead to suppression of cell viability, migration and invasion, as well as increased apoptosis. Immunoprecipitation results indicates HTRA1 might facilitate combination between HDAC6 and α‐tubulin to enhance cell migration by decreasing α‐tubulin acetylation. Besides, HTRA1 knockdown inhibited the growth of xenografts derived from orthotopic implantation of GBM cells and prolonged the survival time of tumor‐bearing mice.ConclusionOur results indicate that HTRA1 promotes the proliferation and migration of GBM cells in vitro and in vivo, and thus may be a potential target for treatment in gliomas.

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Role of Serine Proteases and Inhibitors in Cancer

Cited by 11 publications

References 148 publications

Comparative sera proteomics analysis of differentially expressed proteins in oral squamous cell carcinoma

Comparative sera proteomics analysis of differentially expressed proteins in oral squamous cell carcinoma

SPINT2 controls SARS-CoV-2 viral infection and is associated to disease severity

HTRA1 promotes EMT through the HDAC6/Ac‐α‐tubulin pathway in human GBM cells

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