DDAH1 mediates gastric cancer cell invasion and metastasis <i>via</i> Wnt/β‐catenin signaling pathway

Ye, Jianxin; Xu, Jie; Li, Yun; Huang, Qiang; Huang, Jinsheng; Wang, Jinzhou; Zhong, Wenjing; Lin, Xi Zhang; Chen, Wan-Nan; Lin, Xu

doi:10.1002/1878-0261.12089

Cited by 34 publications

(33 citation statements)

References 34 publications

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“…FGF2 is implicated in fibrosis, although both profibrotic [51] and antifibrotic [52] activity has been attributed to this growth factor. The DDAHs association with FGF2 warrants further investigation as well, as DDAH2 has recently been shown to alleviate fibrosis associated with diabetic cardiomyopathy [38] and DDAH1 to inhibit the Wnt/β-catenin pathway, EMT, and gastric cancer cell migration [53]. Clouding matters, DDAH1 has promoted the migration of prostate cancer cells [54].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings

Krzystek−Korpacka

Fleszar

Bednarz−Misa

et al. 2020

IJMS

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L-arginine/nitric oxide pathway in Crohn's disease (CD) and ulcerative colitis (UC) is poorly investigated. The aim of current study is to quantify pathway serum metabolites in 52 CD (40 active), 48 UC (33 active), and 18 irritable bowel syndrome patients and 40 controls using mass spectrometry and at determining mRNA expression of pathway-associated enzymes in 91 bowel samples. Arginine and symmetric dimethylarginine decreased (p < 0.05) in active-CD (129 and 0.437 µM) compared to controls (157 and 0.494 µM) and active-UC (164 and 0.52 µM). Citrulline and dimethylamine increased (p < 0.05) in active-CD (68.7 and 70.9 µM) and active-UC (65.9 and 73.9 µM) compared to controls (42.7 and 50.4 µM). Compared to normal, CD-inflamed small bowel had downregulated (p < 0.05) arginase-2 by 2.4-fold and upregulated dimethylarginine dimethylaminohydrolase (DDAH)-2 (1.5-fold) and arginine N-methyltransferase (PRMT)-2 (1.6-fold). Quiescent-CD small bowel had upregulated (p < 0.05) arginase-2 (1.8-fold), DDAH1 (2.9-fold), DDAH2 (1.5-fold), PRMT1 (1.5-fold), PRMT2 (1.7-fold), and PRMT5 (1.4-fold). Pathway enzymes were upregulated in CD-inflamed/quiescent and UC-inflamed colon as compared to normal. Compared to inflamed, quiescent CD-colon had upregulated DDAH1 (5.7-fold) and ornithine decarboxylase (1.6-fold). Concluding, the pathway is deregulated in CD and UC, also in quiescent bowel, reflecting inflammation severity and angiogenic potential. Functional analysis of PRMTs and DDAHs as potential targets for therapy is warranted.

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Section: Discussionmentioning

confidence: 99%

Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings

Krzystek−Korpacka

Fleszar

Bednarz−Misa

et al. 2020

IJMS

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“…7D). By contrast, in DMSO-treated shGFP-transfected SGC-7901 cell groups, tumor volume was approximately 400 mm 3 and PGD2 treatment further reduced tumor volume ( Fig. 7D).…”

Section: Pgd2/ptgdr2 Signaling Inhibited Tumor Growth and Tumorigenesmentioning

confidence: 91%

PGD2/PTGDR2 Signaling Restricts the Self-Renewal and Tumorigenesis of Gastric Cancer

Zhang

Bie

et al. 2018

Stem Cells

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The antitumor effect of prostaglandin D2 (PGD2) on gastric cancer (GC) has been known for decades. However, the mechanism of PGD2's control of GC growth is unclear. Cancer stem cells (CSCs) are implicated in tumor neovascularization, invasiveness, and therapeutic resistance. Herein, we discovered that signaling between PGD2 and its receptor (PTGDR2) has the ability to restrict the self-renewal of GC cells in vitro and suppress tumor growth and metastasis in vivo. To obtain these findings, we first determined that PGD2 synthase (L-PTGDS) and PTGDR2 expression were lower in GC tissues than adjacent tissues and was associated with the patients' prognosis. Moreover, the expression of L-PTGDS and PTGDR2 was negatively correlated with the GC-CSC markers Sall4 and Lgr5 in GC tissues. Second, L-PTGDS and PTGDR2 expression were knocked down in CSC-like cells, resulting in enhanced expression of CSC markers and self-renewal ability. Direct PGD2 stimulation and L-PTGDS overexpression produced the opposite effect. Thirdly, PGD2 inhibited tumor growth and incidence rate in a subcutaneous tumor model and suppressed liver and mesenteric metastasis in a peritoneal metastasis model. Interfering with the expression of PTGDR2 reversed these effects in vivo. Last, a mechanistic study found that PGD2 inhibited STAT3 phosphorylation and nuclear expression. Further experiments revealed that the inhibitory effect of PGD2 on the expression of CSC markers disappeared after mutations were introduced into STAT3 phosphorylation (Thr705) site. In short, this study reveals a novel function of PGD2/PTGDR2 signaling on CSC regulation and provides a new way to control the development of GC. Stem Cells 2018;36:990-1003.

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“…Up to date, protein dysregulation have been described only in GC tissues but not in GC blood for (1) CDCP1 [49], (2) DDAH1 [50], (3) PPIA [51], and (4) HMOX1 [52,53]. (1) CDCP1 is a transmembrane glycoprotein and its engineered overexpression in gastric cell lines was shown to increase cell migration and invasion [49,54].…”

Section: Discussionmentioning

confidence: 99%

A Targeted Proteomics Approach Reveals a Serum Protein Signature as Diagnostic Biomarker for Resectable Gastric Cancer

et al. 2019

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Background: Gastric cancer (GC) is the third leading cause of cancer death. Early detection is a key factor to reduce its mortality. Methods: We retrospectively collected pre-and postoperative serum samples as well as tumour tissues and adjacent normal tissues from 100 GC patients. Serum samples from non-cancerous patients were served as controls (n = 50). A high-throughput protein detection technology, multiplex proximity extension assays (PEA), was applied to measure levels of over 300 proteins. Alteration of each protein was analysed by univariate analysis. Elastic-net logistic regression was performed to select serum proteins into the diagnostic model. Findings: We identified 19 serum proteins (CEACAM5, CA9, MSLN, CCL20, SCF, TGF-alpha, MMP-1, MMP-10, IGF-1, CDCP1, PPIA, DDAH-1, HMOX-1, FLI1, IL-7, ZBTB-17, APBB1IP, KAZALD-1, and ADAMTS-15) that together distinguish GC cases from controls with a diagnostic sensitivity of 93%, specificity of 100%, and area under receiver operating characteristic curve (AUC) of 0·99 (95% CI: 0·98-1). Moreover, the 19-serum protein signature provided an increased diagnostic capacity in patients at TNM I-II stage (sensitivity 89%, specificity 100%, AUC 0·99) and in patients with high microsatellite instability (MSI) (91%, 98%, and 0·99) compared to individual proteins. These promising results will inspire a large-scale independent cohort study to be pursued for validating the proposed protein signature. Interpretation: Based on targeted proteomics and elastic-net logistic regression, we identified a 19-serum protein signature which could contribute to clinical GC diagnosis, especially for patients at early stage and those with high MSI. Fund: This study was supported by a European H2020-Marie Skłodowska-Curie Innovative Training Networks grant (316,929, GastricGlycoExplorer). Funder had no influence on trial design, data evaluation, and interpretation.EBioMedicine 44 (2019) 322-333Abbreviations: ADAMTS-15, A disintegrin and metalloproteinase with thrombospondin motifs 15; APBB1IP, Amyloid beta A4 precursor protein-binding family B member 1-interacting protein; CA9, Carbonic anhydrase 9; CCL20, C-C motif chemokine 20; CDCP1, CUB domain-containing protein 1; CEACAM5, Carcinoembryonic antigen-related cell adhesion molecule 5; DDAH1, dimethylarginine dimethylaminohydrolase 1; FLI-1, Friend leukemia integration 1 transcription factor; GCNT1, beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-Nacetylglucosaminyltransferase; HMOX1, Heme oxygenase 1; IGF1, Insulin-like growth factor I; IL-7, Interleukin-7; KAZALD1, Kazal-type serine protease inhibitor domain containing protein 1; MSLN, Mesothelin; MMP-1, Matrix metalloproteinase-1; MMP-10, Matrix metalloproteinase-10; PPIA, Peptidyl-prolyl cis-trans isomerase A; SCF, Stem cell factor/KIT ligand; TGF alpha, Transforming growth factor alpha; ZBTB-17, Zinc finger and BTB domain-containing protein 17.

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DDAH1 mediates gastric cancer cell invasion and metastasis via Wnt/β‐catenin signaling pathway

Cited by 34 publications

References 34 publications

Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings

Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings

PGD2/PTGDR2 Signaling Restricts the Self-Renewal and Tumorigenesis of Gastric Cancer

A Targeted Proteomics Approach Reveals a Serum Protein Signature as Diagnostic Biomarker for Resectable Gastric Cancer

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