Down‐regulation of <scp>LPA</scp> receptor 5 contributes to aberrant <scp>LPA</scp> signalling in <scp>EBV</scp>‐associated nasopharyngeal carcinoma

Yap, Lee Fah; Velapasamy, Sharmila; Lee, Hui Min; Thavaraj, Selvam; Rajadurai, Pathmanathan; Wei, Wenbin; Vrzalikova, Katerina; Ibrahim, Maha; Khoo, Alan Soo Beng; Tsao, Sai Wah; Paterson, Ian C.; Taylor, Graham S.; Dawson, Christopher W.; Murray, Paul G.

doi:10.1002/path.4460

Cited by 16 publications

(14 citation statements)

References 24 publications

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“…Consistent with this, HOPX has been shown to suppress c-fos transcription in a SRF dependent manner in endometrial and breast cancer cell lines25. These results are particularly noteworthy because we have recently observed that LPA signalling is aberrantly activated in NPC18. In addition, we found that re-expression of HOPX sensitised OSCC and NPC cells to UVA-induced apoptosis, confirming a functional role for HOPX in mediating the response to DNA damage.…”

Section: Discussionsupporting

confidence: 78%

“…5B) in both cell lines compared to their respective controls. LPA can induce SRF whose activity is inhibited by HOPX17 and we have previously shown that LPA is a motility factor for both OSCC and NPC cells (unpublished data;18). Therefore, we next investigated whether HOPX is involved in LPA-mediated migration and found that the migration of both HOPX-expressing H376 and HONE1 cells was significantly reduced compared to the vector controls (p < 0.05; Fig.…”

Section: Resultsmentioning

confidence: 87%

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HOPX functions as a tumour suppressor in head and neck cancer

Yap

Lai

Patmanathan

et al. 2016

Sci Rep

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Head and neck squamous cell carcinoma (HNSCC) is generalized term that encompasses a diverse group of cancers that includes tumours of the oral cavity (OSCC), oropharynx (OPSCC) and nasopharynx (NPC). Genetic alterations that are common to all HNSCC types are likely to be important for squamous carcinogenesis. In this study, we have investigated the role of the homeodomain-only homeobox gene, HOPX, in the pathogenesis of HNSCC. We show that HOPX mRNA levels are reduced in OSCC and NPC cell lines and tissues and there is a general reduction of HOPX protein expression in these tumours and OPSCCs. HOPX promoter methylation was observed in a subset of HNSCCs and was associated with a worse overall survival in HPV negative tumours. RNAseq analysis of OSCC cells transfected with HOPX revealed a widespread deregulation of the transcription of genes related to epithelial homeostasis and ectopic over-expression of HOPX in OSCC and NPC cells inhibited cell proliferation, plating efficiency and migration, and enhanced sensitivity to UVA-induced apoptosis. Our results demonstrate that HOPX functions as a tumour suppressor in HNSCC and suggest a central role for HOPX in suppressing epithelial carcinogenesis.

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Section: Discussionsupporting

confidence: 78%

Section: Resultsmentioning

confidence: 87%

HOPX functions as a tumour suppressor in head and neck cancer

Yap

Lai

Patmanathan

et al. 2016

Sci Rep

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“…The present study was unable to validate all 21 key genes and could not solve the problem regarding histological, genetic, clinic biological characteristics and treatments of PTCs, primarily due to fund shortage. However among these genetic targets, LPAR5 was demonstrated to be involved in the pathogenesis of several types of cancer including melanoma, sarcoma, nasopharyngeal carcinoma ( 53 , 58 , 59 ). LPAR5 is lysophosphatidic acid (LPA) receptor 5, encodes a member of the rhodopsin class of G protein-coupled transmembrane receptors ( 60 ).…”

Section: Discussionmentioning

confidence: 99%

Genetic expression profile‑based screening of genes and pathways associated with papillary thyroid carcinoma

Yin

2018

Oncol Lett

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Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer; however, the specific genes and signaling pathways involved in this cancer remain largely unclear. The present study analyzed three profile datasets, GSE6004, GSE29265 and GSE60542, which were comprised of 47 PTC and 41 normal thyroid tissue samples, to identify key genes and pathways associated with PTC. Initially, differentially-expressed genes (DEGs) between PTC and normal thyroid tissue were screened using R 3.4.0 (2017-04-21, R Foundation, Vienna, Austria, ). These DEGs were then clustered by gene ontology functional terms and representative signaling pathways. Additionally, specific key gene nodes were filtered out from a constructed protein-protein interaction (PPI) network. The results identified a total of 423 shared DEGs associated with PTC, including 211 upregulated and 212 downregulated genes. These 423 genes were primarily enriched in glycosaminoglycan binding, sulfur compound binding, heparin binding, enzyme activator activity, peptidase activator activity and hsa04512: Extracellular matrix (ECM)-receptor interaction. A total of 21 central node genes were identified as key genes in the PTC disease process including complement factor D (CFD), Collagen Type I α 1 Chain (COL1A1), Extracellular Matrix Protein 1 (ECM1) and Fibronectin 1 (FN1). These genes are involved in protease binding, G-protein coupled receptor binding, extracellular matrix structural constituent and peptidase regulator activity. To conclude, using bioinformatics analysis, the present study identified candidate DEGs and critical pathways in PTC that may improve the current understanding regarding the underlying mechanisms of PTC. These genes and pathways may be used as potential therapeutic targets of PTC in the future.

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“…The EBV belongs to the Herpes virus family. EBV infection is associated with a series of tumours, such as nasopharyngeal carcinoma, Burkett lymphoma, stomach cancer and non‐Hodgkin's lymphoma, and certain autoimmune diseases in genetically sensitive individuals . Preferable proliferation of γδ T‐cells has been observed in urgent or chronic EBV infections .…”

Section: Discussionmentioning

confidence: 99%

EBV transformation induces overexpression of hMSH2/3/6 on B lymphocytes and enhances γδT‐cell‐mediated cytotoxicity via TCR and NKG2D

Dai

Liu

et al. 2018

Immunology

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The engagement of Epstein-Barr virus (EBV)-induced protein ligands in γδ T-cell-mediated anti-EBV immunity, especially in EBV-associated B-cell malignancies, has not been fully elucidated. Previously we reported the overexpression of human MutS homologue 2 (hMSH2), a stress-inducible protein ligand for human γδ T-cells, on EBV-transformed B lymphoblastic cell lines (B-LCLs). In this study, we first generated EBV-transformed B-LCLs from peripheral blood mononuclear cells of healthy volunteers with B95-8 cellular supernatant and cyclosporine A. Secondly, we demonstrated the significantly elevated cell surface protein expression and mRNA transcription of hMSH2 in EBV-transformed B-LCLs, 3D5 and EBV-positive B lymphoma cell line Daudi and Raji. Thirdly, hMSH2-mediated recognition of EBV-transformed B malignant cells by human γδ T-cells was confirmed by specific antibody blocking and siRNA interference. Both TCRγδ and NKG2D participated in hMSH2-mediated recognition of EBV-transformed B malignant cells. Furthermore, hMSH3 and hMSH6, the companion proteins of hMSH2, along with CD98, were found overexpressed on the surface of EBV-transformed malignant B-cells. We concluded that the induced overexpression of hMSH proteins might serve as early alerting biomarkers emerged in EBV-related B-cell malignances or as potential targets for establishing γδ T-cell-based therapeutic immunotherapies towards EBV infection.

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Down‐regulation of LPA receptor 5 contributes to aberrant LPA signalling in EBV‐associated nasopharyngeal carcinoma

Cited by 16 publications

References 24 publications

HOPX functions as a tumour suppressor in head and neck cancer

HOPX functions as a tumour suppressor in head and neck cancer

Genetic expression profile‑based screening of genes and pathways associated with papillary thyroid carcinoma

EBV transformation induces overexpression of hMSH2/3/6 on B lymphocytes and enhances γδT‐cell‐mediated cytotoxicity via TCR and NKG2D

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