Advertisement

Tumor Biology

, Volume 36, Issue 6, pp 4603–4610 | Cite as

Epigenetic inactivation of SOX1 promotes cell migration in lung cancer

  • Ning Li
  • Suyun Li
Research Article

Abstract

SOX1 is epigenetically inactivated in hepatocellular carcinoma. However, the expression and methylation status of SOX1 in non-small cell lung cancer (NSCLC) remains unknown. The aim of the current study was to investigate whether the promoter hypermethylation of SOX1 is involved in human lung carcinogenesis. We first detected the expression of SOX1 protein in a tissue microarray (TMA) of primary NSCLC and adjacent normal lung tissue specimens using immunohistochemical staining with a specific anti-SOX1 antibody. Methylation of the promoter region of SOX1 in lung cancer tissues was determined by bisulfite sequencing PCR (BSP). In the present study, we found that the SOX1 promoter was fully or partially methylated in 40 of 60 (66.7 %) tumor tissues but not in the majority 15 of 60 (25 %) of normal tissues. A statistically significant inverse association was found between SOX1 methylation status and expression of the SOX1 in tumor tissues (P = 0.003). We further demonstrate that restoration of SOX1 inhibited cell migration by regulating actin cytoskeletal remodeling. Our results suggest that SOX1 is epigenetically silenced in the majority of NSCLC and restoration of SOX1 inhibited cell migration by regulating actin cytoskeletal remodeling in NSCLC.

Keywords

Non-small cell lung cancer SOX1 Methylation 

Notes

Conflicts of interest

None.

References

  1. 1.
    Kan L, Israsena N, Zhang Z, Hu M, Zhao LR, Jalali A, et al. Sox1 acts through multiple independent pathways to promote neurogenesis. Dev Biol. 2004;269(2):580–94.CrossRefPubMedGoogle Scholar
  2. 2.
    Shih YL, Hsieh CB, Yan MD, Tsao CM, Hsieh TY, Liu CH, et al. Frequent concomitant epigenetic silencing of SOX1 and secreted frizzled-related proteins (SFRPs) in human hepatocellular carcinoma. J Gastroenterol Hepatol. 2013;28(3):551–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Tsao CM, Yan MD, Shih YL, Yu PN, Kuo CC, Lin WC, et al. SOX1 functions as a tumor suppressor by antagonizing the WNT/beta-catenin signaling pathway in hepatocellular carcinoma. Hepatol Baltimore Md. 2012;56(6):2277–87.CrossRefGoogle Scholar
  4. 4.
    Lai HC, Lin YW, Huang TH, Yan P, Huang RL, Wang HC, et al. Identification of novel DNA methylation markers in cervical cancer. Int J Cancer. 2008;123(1):161–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Su HY, Lai HC, Lin YW, Chou YC, Liu CY, Yu MH. An epigenetic marker panel for screening and prognostic prediction of ovarian cancer. Int J Cancer. 2009;124(2):387–93.CrossRefPubMedGoogle Scholar
  6. 6.
    Li N, Li X, Li S, Zhou S, Zhou Q. Cisplatin-induced downregulation of SOX1 increases drug resistance by activating autophagy in non-small cell lung cancer cell. Biochem Biophys Res Commun. 2013;439(2):187–90.CrossRefPubMedGoogle Scholar
  7. 7.
    Pu J, Mao Y, Lei X, Yan Y, Lu X, Tian J, et al. FERM domain containing protein 7 interacts with the Rho GDP dissociation inhibitor and specifically activates Rac1 signaling. PLoS One. 2013;8(8):e73108.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Koga T, Takeshita M, Yano T, Maehara Y, Sueishi K. CHFR hypermethylation and EGFR mutation are mutually exclusive and exhibit contrastive clinical backgrounds and outcomes in non-small cell lung cancer. Int J Cancer. 2011;128(5):1009–17.CrossRefPubMedGoogle Scholar
  9. 9.
    Hong KM, Yang SH, Chowdhuri SR, Player A, Hames M, Fukuoka J, et al. Inactivation of LLC1 gene in nonsmall cell lung cancer. Int J Cancer. 2007;120(11):2353–8.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Lin YW, Tsao CM, Yu PN, Shih YL, Lin CH, Yan MD. SOX1 suppresses cell growth and invasion in cervical cancer. Gynecol Oncol. 2013;131(1):174–81.CrossRefPubMedGoogle Scholar
  11. 11.
    Gardberg M, Kaipio K, Lehtinen L, Mikkonen P, Heuser VD, Talvinen K, et al. FHOD1, a formin upregulated in epithelial-mesenchymal transition, participates in cancer cell migration and invasion. PLoS One. 2013;8(9):e74923.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Wilson AL, Schrecengost RS, Guerrero MS, Thomas KS, Bouton AH. Breast cancer antiestrogen resistance 3 (BCAR3) promotes cell motility by regulating actin cytoskeletal and adhesion remodeling in invasive breast cancer cells. PLoS One. 2013;8(6):e65678.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Ridley AJ. Life at the leading edge. Cell. 2011;145(7):1012–22.CrossRefPubMedGoogle Scholar
  14. 14.
    Valderrama F, Thevapala S, Ridley AJ. Radixin regulates cell migration and cell-cell adhesion through Rac1. J Cell Sci. 2012;125(Pt 14):3310–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Schlunck G, Damke H, Kiosses WB, Rusk N, Symons MH, Waterman-Storer CM, et al. Modulation of Rac localization and function by dynamin. Mol Biol Cell. 2004;15(1):256–67.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Respiratory MedicineThe First Affiliated Hospital of Henan University of Traditional Chinese MedicineZhengzhouChina

Personalised recommendations