Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
November-2017 Volume 14 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November-2017 Volume 14 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

TIAM1 inhibits lung fibroblast differentiation in pulmonary fibrosis

  • Authors:
    • Zhicheng Huang
    • Shuangyan Sun
    • Changliang Yang
    • Jun Zheng
    • Yingji Nan
    • Ruikun Zhao
    • Zhiguo Lang
    • Hang Li
    • Lixia Ma
  • View Affiliations / Copyright

    Affiliations: Department of Radiology, Jilin Province Cancer Hospital, Changchun, Jilin 130012, P.R. China, Department of Thoracic Oncology, Jilin Province Cancer Hospital, Changchun, Jilin 130012, P.R. China, The First Division of Chest Medicine, Jilin Province Cancer Hospital, Changchun, Jilin 130012, P.R. China
    Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4254-4262
    |
    Published online on: August 24, 2017
       https://doi.org/10.3892/etm.2017.5024
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The differentiation of fibroblasts to myofibroblasts is critical for the development of idiopathic pulmonary fibrosis (IPF). T‑cell lymphoma invasion and metastasis 1 (TIAM1) is known to be associated with amyotrophic lateral sclerosis 1 and colorectal cancer; however, its role in IPF is unclear. The aim of the present study was to investigate the expression and roles of TIAM1 in lung fibroblasts during pulmonary fibrosis. It was demonstrated that TIAM1 expression was significantly increased in fibrotic lung tissue and lung fibroblasts from bleomycin (BLM)‑treated mice compared with control mice (P<0.05). TIAM1 expression and differentiation were significantly upregulated in human lung fibroblasts challenged with transforming growth factor‑β (TGF‑β) compared with unchallenged cells (P<0.05). Furthermore, inhibition of the nuclear factor (NF)‑κB signaling pathway significantly attenuated TGF‑β‑induced TIAM1 expression and decreased fibroblast differentiation in human lung fibroblasts (P<0.05). Similarly, overexpression of TIAM1 significantly inhibited TGF‑β‑induced fibroblast differentiation, as indicated by decreased expression of fibronectin and α‑smooth muscle actin (SMA; P<0.05). The results of the present study also demonstrated that TIAM1 knockdown increased TGF‑β‑induced fibroblast differentiation (P<0.05). These findings suggest that TIAM1 expression is associated with lung fibroblast differentiation in pulmonary fibrosis via an NF‑κB‑dependent pathway, and that TIAM1 inhibits lung fibroblast differentiation in pulmonary fibrosis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Bourguignon LY, Zhu H, Shao L and Chen YW: Ankyrin-Tiam1 interaction promotes Rac1 signaling and metastatic breast tumor cell invasion and migration. J Cell Biol. 150:177–191. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Ceccarelli DF, Blasutig IM, Goudreault M, Li Z, Ruston J, Pawson T and Sicheri F: Non-canonical interaction of phosphoinositides with pleckstrin homology domains of Tiam1 and ArhGAP9. J Biol Chem. 282:13864–13874. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Leeuwen FN, Kain HE, Kammen RA, Michiels F, Kranenburg OW and Collard JG: The guanine nucleotide exchange factor Tiam1 affects neuronal morphology; opposing roles for the small GTPases Rac and Rho. J Cell Biol. 139:797–807. 1997. View Article : Google Scholar : PubMed/NCBI

4 

Paliwal S, Ho N, Parker D and Grossman SR: CtBP2 promotes human cancer cell migration by transcriptional activation of tiam1. Genes Cancer. 3:481–490. 2012.PubMed/NCBI

5 

Wang HM and Wang J: Expression of Tiam1 in lung cancer and its clinical significance. Asian Pac J Cancer Prev. 13:613–615. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Vaughan L, Tan CT, Chapman A, Nonaka D, Mack NA, Smith D, Booton R, Hurlstone AF and Malliri A: HUWE1 ubiquitylates and degrades the RAC activator TIAM1 promoting cell-cell adhesion disassembly, migration, and invasion. Cell Rep. 10:88–102. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Minard ME, Herynk MH, Collard JG and Gallick GE: The guanine nucleotide exchange factor Tiam1 increases colon carcinoma growth at metastatic sites in an orthotopic nude mouse model. Oncogene. 24:2568–2573. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Mertens AE, Pegtel DM and Collard JG: Tiam1 takes PARt in cell polarity. Trends Cell Biol. 16:308–316. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Desai LP, Chapman KE and Waters CM: Mechanical stretch decreases migration of alveolar epithelial cells through mechanisms involving Rac1 and Tiam1. Am J Physiol Lung Cell Mol Physiol. 295:L958–L965. 2008. View Article : Google Scholar : PubMed/NCBI

10 

The Lancet Respiratory Medicine: The changing landscape of idiopathic pulmonary fibrosis. Lancet Respir Med. 2:5072014. View Article : Google Scholar : PubMed/NCBI

11 

Wynn TA: Cellular and molecular mechanisms of fibrosis. J Pathol. 214:199–210. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Huang LS and Natarajan V: Sphingolipids in pulmonary fibrosis. Adv Biol Regul. 57:55–63. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Wynn TA: Integrating mechanisms of pulmonary fibrosis. J Exp Med. 208:1339–1350. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Leask A and Abraham DJ: TGF-beta signaling and the fibrotic response. FASEB J. 18:816–827. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Sime PJ, Xing Z, Graham FL, Csaky KG and Gauldie J: Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung. J Clin Invest. 100:768–776. 1997. View Article : Google Scholar : PubMed/NCBI

16 

Xu P, Liu J and Derynck R: Post-translational regulation of TGF-β receptor and Smad signaling. FEBS Lett. 586:1871–1884. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Song N, Liu J, Shaheen S, Du L, Proctor M, Roman J and Yu J: Vagotomy attenuates bleomycin-induced pulmonary fibrosis in mice. Sci Rep. 5:134192015. View Article : Google Scholar : PubMed/NCBI

19 

Choi SH, Kim M, Lee HJ, Kim EH, Kim CH and Lee YJ: Effects of NOX1 on fibroblastic changes of endothelial cells in radiation-induced pulmonary fibrosis. Mol Med Rep. 13:4135–4142. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Minard ME, Kim LS, Price JE and Gallick GE: The role of the guanine nucleotide exchange factor Tiam1 in cellular migration, invasion, adhesion and tumor progression. Breast Cancer Res Treat. 84:21–32. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Liu S, Li Y, Qi W, Zhao Y, Huang A, Sheng W, Lei B, Lin P, Zhu H, Li W and Shen H: Expression of Tiam1 predicts lymph node metastasis and poor survival of lung adenocarcinoma patients. Diagn Pathol. 9:692014. View Article : Google Scholar : PubMed/NCBI

22 

Du X, Wang S, Lu J, Wang Q, Song N, Yang T, Dong R, Zang L, Yang Y, Wu T and Wang C: Clinical value of Tiam1-Rac1 signaling in primary gallbladder carcinoma. Med Oncol. 29:1873–1878. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Engers R, Mueller M, Walter A, Collard JG, Willers R and Gabbert HE: Prognostic relevance of Tiam1 protein expression in prostate carcinomas. Br J Cancer. 95:1081–1086. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Huang J, Ye X, Guan J, Chen B, Li Q, Zheng X, Liu L, Wang S, Ding Y, Ding Y and Chen L: Tiam1 is associated with hepatocellular carcinoma metastasis. Int J Cancer. 132:90–100. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Ding Y, Chen B, Wang S, Zhao L, Chen J, Ding Y, Chen L and Luo R: Overexpression of Tiam1 in hepatocellular carcinomas predicts poor prognosis of HCC patients. Int J Cancer. 124:653–658. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Liu L, Wu DH and Ding YQ: Tiam1 gene expression and its significance in colorectal carcinoma. World J Gastroenterol. 11:705–707. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Nho RS and Polunovsky V: Translational control of the fibroblast-extracellular matrix association: An application to pulmonary fibrosis. Translation (Austin). 1:e239342013.PubMed/NCBI

28 

Darby IA, Laverdet B, Bonté F and Desmoulieré A: Fibroblasts and myofibroblasts in wound healing. Clin Cosmet Investig Dermatol. 7:301–311. 2014.PubMed/NCBI

29 

Gohda E, Matsunaga T, Kataoka H, Takebe T and Yamamoto I: Induction of hepatocyte growth factor in human skin fibroblasts by epidermal growth factor, platelet-derived growth factor and fibroblast growth factor. Cytokine. 6:633–640. 1994. View Article : Google Scholar : PubMed/NCBI

30 

Strutz F, Zeisberg M, Renziehausen A, Raschke B, Becker V, van Kooten C and Müller G: TGF-beta 1 induces proliferation in human renal fibroblasts via induction of basic fibroblast growth factor (FGF-2). Kidney Int. 59:579–592. 2001. View Article : Google Scholar : PubMed/NCBI

31 

Andre F and Cortés J: Rationale for targeting fibroblast growth factor receptor signaling in breast cancer. Breast Cancer Res Treat. 150:1–8. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Song T, Dou C, Jia Y, Tu K and Zheng X: TIMP-1 activated carcinoma-associated fibroblasts inhibit tumor apoptosis by activating SDF1/CXCR4 signaling in hepatocellular carcinoma. Oncotarget. 6:12061–12079. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Mizuno K, Mataki H, Seki N, Kumamoto T, Kamikawaji K and Inoue H: MicroRNAs in non-small cell lung cancer and idiopathic pulmonary fibrosis. J Hum Genet. 62:57–65. 2017. View Article : Google Scholar : PubMed/NCBI

34 

Stella GM, Inghilleri S, Pignochino Y, Zorzetto M, Oggionni T, Morbini P and Luisetti M: Activation of oncogenic pathways in idiopathic pulmonary fibrosis. Transl Oncol. 7:650–655. 2014. View Article : Google Scholar : PubMed/NCBI

35 

Archontogeorgis K, Steiropoulos P, Tzouvelekis A, Nena E and Bouros D: Lung cancer and interstitial lung diseases: A systematic review. Pulm Med. 2012:3159182012. View Article : Google Scholar : PubMed/NCBI

36 

Li Y, Jiang D, Liang J, Meltzer EB, Gray A, Miura R, Wogensen L, Yamaguchi Y and Noble PW: Severe lung fibrosis requires an invasive fibroblast phenotype regulated by hyaluronan and CD44. J Exp Med. 208:1459–1471. 2011. View Article : Google Scholar : PubMed/NCBI

37 

Parnaud G, Hammar E, Ribaux P, Donath MY, Berney T and Halban PA: Signaling pathways implicated in the stimulation of beta-cell proliferation by extracellular matrix. Mol Endocrinol. 23:1264–1271. 2009. View Article : Google Scholar : PubMed/NCBI

38 

Hammar EB, Irminger JC, Rickenbach K, Parnaud G, Ribaux P, Bosco D, Rouiller DG and Halban PA: Activation of NF-kappaB by extracellular matrix is involved in spreading and glucose-stimulated insulin secretion of pancreatic beta cells. J Biol Chem. 280:30630–30637. 2005. View Article : Google Scholar : PubMed/NCBI

39 

Sun X, Chen E, Dong R, Chen W and Hu Y: Nuclear factor (NF)-κB p65 regulates differentiation of human and mouse lung fibroblasts mediated by TGF-β. Life Sci. 122:8–14. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Huang Z, Sun S, Yang C, Zheng J, Nan Y, Zhao R, Lang Z, Li H and Ma L: TIAM1 inhibits lung fibroblast differentiation in pulmonary fibrosis. Exp Ther Med 14: 4254-4262, 2017.
APA
Huang, Z., Sun, S., Yang, C., Zheng, J., Nan, Y., Zhao, R. ... Ma, L. (2017). TIAM1 inhibits lung fibroblast differentiation in pulmonary fibrosis. Experimental and Therapeutic Medicine, 14, 4254-4262. https://doi.org/10.3892/etm.2017.5024
MLA
Huang, Z., Sun, S., Yang, C., Zheng, J., Nan, Y., Zhao, R., Lang, Z., Li, H., Ma, L."TIAM1 inhibits lung fibroblast differentiation in pulmonary fibrosis". Experimental and Therapeutic Medicine 14.5 (2017): 4254-4262.
Chicago
Huang, Z., Sun, S., Yang, C., Zheng, J., Nan, Y., Zhao, R., Lang, Z., Li, H., Ma, L."TIAM1 inhibits lung fibroblast differentiation in pulmonary fibrosis". Experimental and Therapeutic Medicine 14, no. 5 (2017): 4254-4262. https://doi.org/10.3892/etm.2017.5024
Copy and paste a formatted citation
x
Spandidos Publications style
Huang Z, Sun S, Yang C, Zheng J, Nan Y, Zhao R, Lang Z, Li H and Ma L: TIAM1 inhibits lung fibroblast differentiation in pulmonary fibrosis. Exp Ther Med 14: 4254-4262, 2017.
APA
Huang, Z., Sun, S., Yang, C., Zheng, J., Nan, Y., Zhao, R. ... Ma, L. (2017). TIAM1 inhibits lung fibroblast differentiation in pulmonary fibrosis. Experimental and Therapeutic Medicine, 14, 4254-4262. https://doi.org/10.3892/etm.2017.5024
MLA
Huang, Z., Sun, S., Yang, C., Zheng, J., Nan, Y., Zhao, R., Lang, Z., Li, H., Ma, L."TIAM1 inhibits lung fibroblast differentiation in pulmonary fibrosis". Experimental and Therapeutic Medicine 14.5 (2017): 4254-4262.
Chicago
Huang, Z., Sun, S., Yang, C., Zheng, J., Nan, Y., Zhao, R., Lang, Z., Li, H., Ma, L."TIAM1 inhibits lung fibroblast differentiation in pulmonary fibrosis". Experimental and Therapeutic Medicine 14, no. 5 (2017): 4254-4262. https://doi.org/10.3892/etm.2017.5024
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team