PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells

He, Feng; Chen, Hairong; Probst‐Kepper, Michael; Geffers, Robert; Eifes, Serge; Sol, Antonio del; Schughart, Klaus; Zeng, An‐Ping; Balling, Rudi

doi:10.1038/msb.2012.56

Cited by 58 publications

(72 citation statements)

References 80 publications

(113 reference statements)

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“…This agrees with the results of a recent study that elegantly dissects previously unknown associations of uPA and Treg homeostasis. This study demonstrates that uPA −/− mice are characterized by increased Treg development, yet impaired Treg suppressive function [75]. These results, along with the observations of recent studies, which show that the capacity of Treg to suppress or promote carcinogenesis depends on their activation status [52], [67], [74], suggest that the impaired function of Treg in uPA −/− mice may, at least in part, contribute to their susceptibility in inflammatory-associated colon carcinogenesis.…”

Section: Discussionsupporting

confidence: 76%

Urokinase-Type Plasminogen Activator Deficiency Promotes Neoplasmatogenesis in the Colon of Mice

Karamanavi

Angelopoulou

Lavrentiadou

et al. 2014

Translational Oncology

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Urokinase-type plasminogen activator (uPA) participates in cancer-related biologic processes, such as wound healing and inflammation. The present study aimed to investigate the effect of uPA deficiency on the long-term outcome of early life episodes of dextran sodium sulfate (DSS)–induced colitis in mice. Wild-type (WT) and uPA-deficient (uPA−/−) BALB/c mice were treated with DSS or remained untreated. Mice were necropsied either 1 week or 7 months after DSS treatment. Colon samples were analyzed by histopathology, immunohistochemistry, ELISA, and real-time polymerase chain reaction. At 7 months, with no colitis evident, half of the uPA−/− mice had large colonic polypoid adenomas, whereas WT mice did not. One week after DSS treatment, there were typical DSS-induced colitis lesions in both WT and uPA−/− mice. The affected colon of uPA−/− mice, however, had features of delayed ulcer re-epithelialization and dysplastic lesions of higher grade developing on the basis of a significantly altered mucosal inflammatory milieu. The later was characterized by more neutrophils and macrophages, less regulatory T cells (Treg), significantly upregulated cytokines, including interleukin-6 (IL-6), IL-17, tumor necrosis factor-α, and IL-10, and lower levels of active transforming growth factor–β1 (TGF-β1) compared to WT mice. Dysfunctional Treg, more robust protumorigenic inflammatory events, and an inherited inability to produce adequate amounts of extracellular active TGF-β1 due to uPA deficiency are interlinked as probable explanations for the inflammatory-induced neoplasmatogenesis in the colon of uPA−/− mice.

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Section: Discussionsupporting

confidence: 76%

Urokinase-Type Plasminogen Activator Deficiency Promotes Neoplasmatogenesis in the Colon of Mice

Karamanavi

Angelopoulou

Lavrentiadou

et al. 2014

Translational Oncology

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“…ICOSLG (also known as ICOSL), is important for individual B cells to competitively participate in the germinal center reaction 36 and together with ICOS, is critically involved in type 2 innate lymphoid cells function and homeostasis which can cause allergic asthma 37 ; Correlation network identified PLAU as critical regulator for suppressor function of regulatory T cells. 38 PLAU is overexpressed in many cancer cells, including breast cancer, and plays a crucial role in the metastatic process. [39][40][41] These findings suggest important functions of ICOSLG and PLAU in immune responses, especially for PLAU which was not only significantly upregulated in ESCC tissues, but also significantly associated with overall survival in our results.…”

Section: Discussionmentioning

confidence: 99%

Immune signature profiling identified predictive and prognostic factors for esophageal squamous cell carcinoma

Cao

et al. 2017

OncoImmunology

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Understanding interactions between tumor and the host immune system holds great promise to uncover biomarkers for targeted therapies and clinical outcomes. However, systematical analysis of immune signatures in esophageal squamous cell carcinoma (ESCC) remains largely unstudied. In this study, immune signatures containing 708 immune related genes were curated from mRNA microarray data with tumor and paired normal tissues from 119 ESCC patients. Differential expression and survival analysis were performed with validations from Human Protein Atlas and an independent cohort of 110 ESCC patients by immunohistochemistry staining. We identified a total of 186 significantly dysregulated genes in ESCC, including downregulated genes SPINK5, IL1RN and upregulated genes SPP1 and PLAU, which were further confirmed in Human Protein Atlas data. Moreover, nine immune related genes (ABL1, ATF2, ATG5, C6, CD38, HMGB1, ICOSLG, IL12RB2 and PLAU) were significantly associated with patients' overall survival, among which, prognostic model was built including three independent factors ABL1, CD38 and ICOSLG. Validation by immunohistochemistry staining suggested that combination with tumor infiltrated CD4+ and CD8+ T lymphocytes would yield higher performance in distinguishing cases as high or low risk of unfavorable prognosis. In summary, we profiled the immune status in ESCC and established predictive and prognostic factors for ESCC, which could reflect immune disorders within tumor microenvironments and independently distinguish patients with a high risk of reduced survival, providing novel predictive and therapeutic targets for ESCC patients in the future.

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“…Both He et al [39] and Della Gatta et al [41] used GRNs to identify highly connected nodes as features of interest, and then either rank these hubs, or refine the networks, by use of additional evidence. Interesting hubs prioritized in this way then form the basis of hypotheses that can be subjected to experimental investigation.…”

Section: Discussionmentioning

confidence: 99%

Supervised, semi-supervised and unsupervised inference of gene regulatory networks

Maetschke

Madhamshettiwar

Davis³

et al. 2013

Briefings in Bioinformatics

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125

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Inference of gene regulatory network from expression data is a challenging task. Many methods have been developed to this purpose but a comprehensive evaluation that covers unsupervised, semi-supervised and supervised methods, and provides guidelines for their practical application, is lacking.We performed an extensive evaluation of inference methods on simulated and experimental expression data. The results reveal low prediction accuracies for unsupervised techniques with the notable exception of the Z-SCORE method on knockout data. In all other cases, the supervised approach achieved the highest accuracies and even in a semi-supervised setting with small numbers of only positive samples, outperformed the unsupervised techniques.

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PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells

Abstract: Network-based analysis of transcriptome dynamics during activation in two human T-cell subpopulations identifies key regulators, and reveals that PLAU plays a critical role in both human and murine regulatory T-cell function.

Cited by 58 publications

References 80 publications

Urokinase-Type Plasminogen Activator Deficiency Promotes Neoplasmatogenesis in the Colon of Mice

Urokinase-Type Plasminogen Activator Deficiency Promotes Neoplasmatogenesis in the Colon of Mice

Immune signature profiling identified predictive and prognostic factors for esophageal squamous cell carcinoma

Supervised, semi-supervised and unsupervised inference of gene regulatory networks

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