Tumor Biology

, Volume 37, Issue 2, pp 1663–1669 | Cite as

Epigenetic downregulated ITGBL1 promotes non-small cell lung cancer cell invasion through Wnt/PCP signaling

Original Article


Integrin, beta-like 1 (ITGBL1), is a β-integrin-related extracellular matrix protein which contains ten EGF-like repeats domain. Surprisingly, we screen Oncomine Database and found that ITGBL1 is more commonly downregulated in non-small cell lung cancer (NSCLC) tissues, and the result reminds us to explore its significance in NSCLC. Thus, we retrieved DRUGSURV Database and found that downregulated ITGBL1 predicts a poor prognosis of patients. These results provided us the clues that ITGBL1 might be a tumor suppressor in NSCLC. However, the biological functions of ITGBL1 have not been reported to date. In the current study, we surprisingly found that knockdown of ITGBL1 in NSCLC cell lines could promote cancer cell migration and invasion. Furthermore, recombinant ITGBL1 protein-treated cancer cell could inhibit cell migration and invasion. These results suggested that ITGBL1 plays a suppressive role in NSCLC progression. We further found that the downregulation of ITGBL1 might result from highly expressed miR-576-5p in NSCLC tissues, and the activity of Wnt/PCP signaling was enhanced when the level of ITGBL1 was inhibited. In conclusion, our results suggest that ITGBL1 is a novel tumor suppressor in NSCLC progression.


ITGBL1 NSCLC Tumor suppressor Migration and invasion miR-576-5p Wnt/PCP signaling 


  1. 1.
    Herbst RS, Heymach JV, Lippman SM. Lung cancer. The New England journal of medicine. 2008;359:1367–80.CrossRefPubMedGoogle Scholar
  2. 2.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clinsss. 2013;63:11–30.CrossRefGoogle Scholar
  3. 3.
    Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83(5):584–94.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Little AG, Gay EG, Gaspar LE, Stewart AK. National survey of non-small cell lung cancer in the United States: epidemiology, pathology and patterns of care. Lung Cancer. 2007;57:253–60.CrossRefPubMedGoogle Scholar
  5. 5.
    Lu P, Weaver VM, Werb Z. The extracellular matrix: a dynamic niche in cancer progression. J Cell Biolss. 2012;196:395–406.CrossRefGoogle Scholar
  6. 6.
    Tsunoda T, Furusato B, Takashima Y, Ravulapalli S, Dobi A, Srivastava S, et al. The increased expression of periostin during early stages of prostate cancer and advanced stages of cancer stroma. Prostate. 2009;69:1398–403.CrossRefPubMedGoogle Scholar
  7. 7.
    Tilman G, Mattiussi M, Brasseur F, van Baren N, Decottignies A. Human periostin gene expression in normal tissues, tumors and melanoma: Evidences for periostin production by both stromal and melanoma cells. Mol Cancer. 2007;6:80.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Morra L, Moch H. Periostin expression and epithelial-mesenchymal transition in cancer: a review and an update. Virchows Archiv. 2011;459:465–75.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Fu Y, Feng M-X, Yu J, Ma M-ZM, Liu X-J, Li J, et al. DNA methylation-mediated silencing of matricellular protein dermatopontin promotes hepatocellular carcinoma metastasis by α3β1 integrin-rho gtpase signaling. Oncotarget. 2014;5:6701–15.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Berg RW, Leung E, Gough S, Morris C, Yao WP, Wang SX, et al. Cloning and characterization of a novel beta integrin-related cdna coding for the protein tied ("ten beta integrin egf-like repeat domains") that maps to chromosome band 13q33: a divergent stand-alone integrin stalk structure. Genomics. 1999;56:169–78.CrossRefPubMedGoogle Scholar
  11. 11.
    Esposito V, Baldi A, De Luca A, Groger AM, Loda M, Giordano GG, et al. Prognostic role of the cyclin-dependent kinase inhibitor p27 in non-small cell lung cancer. Cancer Res. 1997;57:3381–5.PubMedGoogle Scholar
  12. 12.
    Katoh M. Wnt/PCP signaling pathway and human cancer (review). Oncol Rep. 2005;14:1583–8.PubMedGoogle Scholar
  13. 13.
    Das PM, Singal R. DNA methylation and cancer. J Clin Oncol. 2004;22:4632–42.CrossRefPubMedGoogle Scholar
  14. 14.
    Kouwenhove M, Kedde M, Agami R. MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Cancer. 2011;11:644–56.CrossRefPubMedGoogle Scholar
  15. 15.
    Sawan C, Herceg Z. Histone modifications and cancer. Adv Genet. 2010;70:57–85.PubMedGoogle Scholar
  16. 16.
    Kanwal R, Gupta S. Epigenetic modifications in cancer. Clin Genet. 2012;81:303–11.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Respiratory MedicineThe First Affiliated Hospital of Nanchang UniversityNanchangChina
  2. 2.Jiangxi Provincial People’s HospitalNanchangChina
  3. 3.Department of Tumor ChemotherapyJiangxi Tumor HospitalNangchangChina
  4. 4.Department of Internal medicineJiangxi Tumor HospitalNangchangChina

Personalised recommendations