Inhibition of SERPINE1 Function Attenuates Wound  Closure in Response to Tissue Injury: A Role for PAI-1 in  Re-Epithelialization and Granulation Tissue Formation

Simone, Tessa M.; Higgins, Paul J.

doi:10.3390/jdb3010011

Cited by 15 publications

(12 citation statements)

References 67 publications

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“…C11_SERPINE1s exhibited increased expression of SERPINE1 , IGF1 , WT1 and CLDN1 , which all promote cell migration and/or wound healing via various mechanisms. 33 – 36 They also expressed collagens, albeit to a lesser extent as C10_COMPs. Additionally, high expression of the pro-angiogenic EGFL6 suggests these cells to exert paracrine functions.…”

Section: Resultsmentioning

confidence: 99%

A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling

et al. 2020

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The stromal compartment of the tumor microenvironment consists of a heterogeneous set of tissue-resident and tumor-infiltrating cells, which are profoundly moulded by cancer cells. An outstanding question is to what extent this heterogeneity is similar between cancers affecting different organs. Here, we profile 233,591 single cells from patients with lung, colorectal, ovary and breast cancer ( n = 36) and construct a pan-cancer blueprint of stromal cell heterogeneity using different single-cell RNA and protein-based technologies. We identify 68 stromal cell populations, of which 46 are shared between cancer types and 22 are unique. We also characterise each population phenotypically by highlighting its marker genes, transcription factors, metabolic activities and tissue-specific expression differences. Resident cell types are characterised by substantial tissue specificity, while tumor-infiltrating cell types are largely shared across cancer types. Finally, by applying the blueprint to melanoma tumors treated with checkpoint immunotherapy and identifying a naïve CD4 + T-cell phenotype predictive of response to checkpoint immunotherapy, we illustrate how it can serve as a guide to interpret scRNA-seq data. In conclusion, by providing a comprehensive blueprint through an interactive web server, we generate the first panoramic view on the shared complexity of stromal cells in different cancers.

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Section: Resultsmentioning

confidence: 99%

A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling

et al. 2020

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“…SERPINE1 encodes PAI-1, a single chain glycoprotein and a class E member of the serine protease inhibitor (SERPIN). PAI-1 functions as a central regulator of various injury-initiated cellular processes including cell migration, growth, senescence and survival in several organ sites ( Simone & Higgins, 2015 ). Cellular senescence can be regarded as the physiological endstate of the proliferative capacity of cells.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant-rich leaf extract ofBarringtonia racemosasignificantly alters thein vitroexpression of genes encoding enzymes that are involved in methylglyoxal degradation III

Kong

Aziz

Razali

et al. 2016

PeerJ

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BackgroundBarringtonia racemosa is a medicinal plant belonging to the Lecythidaceae family. The water extract of B. racemosa leaf (BLE) has been shown to be rich in polyphenols. Despite the diverse medicinal properties of B. racemosa, information on its major biological effects and the underlying molecular mechanisms are still lacking.MethodsIn this study, the effect of the antioxidant-rich BLE on gene expression in HepG2 cells was investigated using microarray analysis in order to shed more light on the molecular mechanism associated with the medicinal properties of the plant.ResultsMicroarray analysis showed that a total of 138 genes were significantly altered in response to BLE treatment (p < 0.05) with a fold change difference of at least 1.5. SERPINE1 was the most significantly up-regulated gene at 2.8-fold while HAMP was the most significantly down-regulated gene at 6.5-fold. Ingenuity Pathways Analysis (IPA) revealed that “Cancer, cell death and survival, cellular movement” was the top network affected by the BLE with a score of 44. The top five canonical pathways associated with BLE were Methylglyoxal Degradation III followed by VDR/RXR activation, TR/RXR activation, PXR/RXR activation and gluconeogenesis. The expression of genes that encode for enzymes involved in methylglyoxal degradation (ADH4, AKR1B10 and AKR1C2) and glycolytic process (ENO3, ALDOC and SLC2A1) was significantly regulated. Owing to the Warburg effect, aerobic glycolysis in cancer cells may increase the level of methylglyoxal, a cytotoxic compound.ConclusionsBLE has the potential to be developed into a novel chemopreventive agent provided that the cytotoxic effects related to methylglyoxal accumulation are minimized in normal cells that rely on aerobic glycolysis for energy supply.

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“…ECM degradation facilitates the migration of tumor cells to other tissues and structures. SERPINE1 regulates this process and the adhesion/deadhesion balance of cells to the ECM, which is essential to control and promote tumor cell migration [ 16 , 17 ]. A high expression of uPA/uPAR and SERPINE1 has been observed in numerous cancer types, being associated with poor patient prognosis [ 12 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy

et al. 2016

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There is strong evidence supporting the role of the plasminogen activator system in head and neck squamous cell carcinoma (HNSCC), particularly of its uPA (urokinase plasminogen activator) / uPAR (urokinase plasminogen activator receptor) and SERPINE1 components. Overexpression of uPA/uPAR and SERPINE1 enhances tumor cell migration and invasion and plays a key role in metastasis development, conferring poor prognosis. The apparent paradox of uPA/uPAR and its inhibitor SERPINE1 producing similar effects is solved by the identification of SERPINE1 activated signaling pathways independent of uPA inhibition. Both uPA/uPAR and SERPINE1 are directly linked to the induction of epithelial-to-mesenchymal transition, the acquisition of stem cell properties and resistance to antitumor agents. The aim of this review is to provide insight on the deregulation of these proteins in all these processes.We also summarize their potential value as prognostic biomarkers or potential drug targets in HNSCC patients. Concomitant overexpression of uPA/uPAR and SERPINE1 is associated with a higher risk of metastasis and could be used to identify patients that would benefit from an adjuvant treatment. In the future, the specific inhibitors of uPA/uPAR and SERPINE1, which are still under development, could be used to design new therapeutic strategies in HNSCCs.

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Inhibition of SERPINE1 Function Attenuates Wound Closure in Response to Tissue Injury: A Role for PAI-1 in Re-Epithelialization and Granulation Tissue Formation

Cited by 15 publications

References 67 publications

A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling

A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling

Antioxidant-rich leaf extract ofBarringtonia racemosasignificantly alters thein vitroexpression of genes encoding enzymes that are involved in methylglyoxal degradation III

uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy

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