Skip to main content

Advertisement

SpringerLink
Log in

Vimentin is a crucial target for anti-metastasis therapy of nasopharyngeal carcinoma

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Nasopharyngeal carcinoma (NPC) is a unique subtype of head and neck cancer, with tendency to spread to regional lymph nodes and distant organs at early stage. Vimentin, a major cytoskeletal protein constituent of the intermediate filament, plays a critical role in the epithelial–mesenchymal transition. Overexpression of vimentin is considered to be a critical prerequisite for metastasis in numerous human cancers. Therefore, targeting vimentin for cancer therapy has gained a lot of interest. In the present study, we detected vimentin expression in NPC tissues and found that overexpression of vimentin is associated with poor prognosis of NPC patients. Silencing of vimentin in NPC CNE2 cells by RNAi suppresses cells migration and invasion in vitro. However, blocking vimentin did not affect cell proliferation of CNE2 cells. In addition, the in vivo metastatic potential of CNE2 cells transfected with Vimentin shRNA was suppressed in a nude mouse model of pulmonary metastasis. Silencing of Vimentin in CNE2 cells leads to a decrease of microvessel density and VEGF, CD31, MMP2, and MMP9 expressions in pulmonary metastatic tumors. Importantly, we found that it is easier for the tumor cells from the high vimentin-expressing pulmonary metastatic tumors to reinvade the microvessel and to form stable tumor plaques attached to the endothelial cells, which resemble the resource of circulating tumor cells and are very hard to eliminate. However, depletion of vimentin inhibits the formation of vascular tumor plaques. Our findings suggest that RNAi-based vimentin silencing may be a potential and promising anti-metastatic therapeutic strategy for NPC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Yan G, Lestari R, Long B, Fan Q, Wang Z, Guo X, Yu J, Hu J, Yang X, Chen C, Liu L, Li X, Purnomoadi A, Achmadi J, Yan X (2016) Comparative Proteomics Analysis Reveals l-Arginine Activates Ethanol Degradation Pathways in HepG2 Cells. Sci Rep 6:23340. doi:10.1038/srep23340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sham JS, Choy D, Wei WI (1990) Nasopharyngeal carcinoma: orderly neck node spread. Int J Radiat Oncol Biol Phys 19(4):929–933

    Article  CAS  PubMed  Google Scholar 

  3. Pan TL, Wang PW, Huang CC, Yeh CT, Hu TH, Yu JS (2012) Network analysis and proteomic identification of vimentin as a key regulator associated with invasion and metastasis in human hepatocellular carcinoma cells. J Proteomics 75(15):4676–4692. doi:10.1016/j.jprot.2012.02.017

    Article  CAS  PubMed  Google Scholar 

  4. Helfand BT, Mendez MG, Murthy SN, Shumaker DK, Grin B, Mahammad S, Aebi U, Wedig T, Wu YI, Hahn KM, Inagaki M, Herrmann H, Goldman RD (2011) Vimentin organization modulates the formation of lamellipodia. Mol Biol Cell 22(8):1274–1289. doi:10.1091/mbc.E10-08-0699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Satelli A, Li S (2011) Vimentin in cancer and its potential as a molecular target for cancer therapy. Cell Mol Life Sci 68(18):3033–3046. doi:10.1007/s00018-011-0735-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mendez MG, Kojima S, Goldman RD (2010) Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition. FASEB J 24(6):1838–1851. doi:10.1096/fj.09-151639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dvorak HF, Brown LF, Detmar M, Dvorak AM (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 146(5):1029–1039

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Sanchez-Tillo E, Liu Y, de Barrios O, Siles L, Fanlo L, Cuatrecasas M, Darling DS, Dean DC, Castells A, Postigo A (2012) EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness. Cell Mol Life Sci 69(20):3429–3456. doi:10.1007/s00018-012-1122-2

    Article  CAS  PubMed  Google Scholar 

  9. Xiang B, Wang W, Li W, Li X, Li G (2012) Differential expression of oxidored nitro domain containing protein 1 (NOR1), in mouse tissues and in normal and cancerous human tissues. Gene 493(1):18–26. doi:10.1016/j.gene.2011.11.039

    Article  CAS  PubMed  Google Scholar 

  10. Xiang B, Yi M, Li W, Wang W, Zheng P, Li X, Li G (2014) Expression of oxidored nitro domain-containing protein 1(NOR1) impairs nasopharyngeal carcinoma cells adaptation to hypoxia and inhibits PDK1 expression. Mol Cell Biochem 393(1–2):293–300. doi:10.1007/s11010-014-2072-9

    Article  CAS  PubMed  Google Scholar 

  11. Wang W, Yi M, Chen S, Li J, Li G, Yang J, Zheng P, Zhang H, Xiong W, McCarthy JB, Li G, Li X, Xiang B (2016) Significance of the NOR1-FOXA1/HDAC2-Slug regulatory network in epithelial-mesenchymal transition of tumor cells. Oncotarget 7(13):16745–16759. doi:10.18632/oncotarget.7778

    Article  PubMed  PubMed Central  Google Scholar 

  12. Wang J, Guo LP, Chen LZ, Zeng YX, Lu SH (2007) Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. Cancer Res 67(8):3716–3724. doi:10.1158/0008-5472.CAN-06-4343

    Article  CAS  PubMed  Google Scholar 

  13. Wang WJ, Wu SP, Liu JB, Shi YS, Huang X, Zhang QB, Yao KT (2013) MYC regulation of CHK1 and CHK2 promotes radioresistance in a stem cell-like population of nasopharyngeal carcinoma cells. Cancer Res 73(3):1219–1231. doi:10.1158/0008-5472.CAN-12-1408

    Article  CAS  PubMed  Google Scholar 

  14. Wang W, Li X, Zhang W, Li W, Yi M, Yang J, Zeng Z, Colvin Wanshura LE, McCarthy JB, Fan S, Zheng P, Chen S, Xiang B, Li G (2014) Oxidored-nitro domain containing protein 1 (NOR1) expression suppresses slug/vimentin but not snail in nasopharyngeal carcinoma: inhibition of EMT in vitro and in vivo in mice. Cancer Lett 348(1–2):109–118. doi:10.1016/j.canlet.2014.03.005

    Article  CAS  PubMed  Google Scholar 

  15. Yi M, Yang J, Li W, Li X, Xiong W, McCarthy JB, Li G, Xiang B (2017) The NOR1/OSCP1 proteins in cancer: from epigenetic silencing to functional characterization of a novel tumor suppressor. J Cancer 8(4):626–635. doi:10.7150/jca.17579

    Article  PubMed  PubMed Central  Google Scholar 

  16. Dauphin M, Barbe C, Lemaire S, Nawrocki-Raby B, Lagonotte E, Delepine G, Birembaut P, Gilles C, Polette M (2013) Vimentin expression predicts the occurrence of metastases in non small cell lung carcinomas. Lung Cancer 81(1):117–122. doi:10.1016/j.lungcan.2013.03.011

    Article  PubMed  Google Scholar 

  17. Cheng Y, Zhou Y, Jiang W, Yang X, Zhu J, Feng D, Wei Y, Li M, Yao F, Hu W, Xiao W, Ling B (2012) Significance of E-cadherin, beta-catenin, and vimentin expression as postoperative prognosis indicators in cervical squamous cell carcinoma. Hum Pathol 43(8):1213–1220. doi:10.1016/j.humpath.2011.08.025

    Article  CAS  PubMed  Google Scholar 

  18. Zelenko Z, Gallagher EJ, Tobin-Hess A, Belardi V, Rostoker R, Blank J, Dina Y, LeRoith D (2017) Silencing vimentin expression decreases pulmonary metastases in a pre-diabetic mouse model of mammary tumor progression. Oncogene 36(10):1394–1403. doi:10.1038/onc.2016.305

    Article  CAS  PubMed  Google Scholar 

  19. Li XH, Chang H, Xu BQ, Tao YL, Gao J, Chen C, Qu C, Zhou S, Liu SR, Wang XH, Zhang WW, Yang X, Zhou SL, Xia YF (2017) An inflammatory biomarker-based nomogram to predict prognosis of patients with nasopharyngeal carcinoma: an analysis of a prospective study. Cancer Med 6(1):310–319. doi:10.1002/cam4.947

    Article  CAS  PubMed  Google Scholar 

  20. Chang ET, Adami HO (2006) The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev 15(10):1765–1777. doi:10.1158/1055-9965.EPI-06-0353

    Article  CAS  PubMed  Google Scholar 

  21. Larsen JE, Nathan V, Osborne JK, Farrow RK, Deb D, Sullivan JP, Dospoy PD, Augustyn A, Hight SK, Sato M, Girard L, Behrens C, Wistuba II, Gazdar AF, Hayward NK, Minna JD (2016) ZEB1 drives epithelial-to-mesenchymal transition in lung cancer. J Clin Invest 126(9):3219–3235. doi:10.1172/JCI76725

    Article  PubMed  PubMed Central  Google Scholar 

  22. Dmello C, Sawant S, Alam H, Gangadaran P, Mogre S, Tiwari R, D’Souza Z, Narkar M, Thorat R, Patil K, Chaukar D, Kane S, Vaidya M (2017) Vimentin regulates differentiation switch via modulation of keratin 14 levels and their expression together correlates with poor prognosis in oral cancer patients. PLoS ONE 12(2):e0172559. doi:10.1371/journal.pone.0172559

    Article  PubMed  PubMed Central  Google Scholar 

  23. Jiu Y, Peranen J, Schaible N, Cheng F, Eriksson JE, Krishnan R, Lappalainen P (2017) Vimentin intermediate filaments control actin stress fiber assembly through GEF-H1 and RhoA. J Cell Sci 130(5):892–902. doi:10.1242/jcs.196881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Woodham EF, Paul NR, Tyrrell B, Spence HJ, Swaminathan K, Scribner MR, Giampazolias E, Hedley A, Clark W, Kage F, Marston DJ, Hahn KM, Tait SW, Larue L, Brakebusch CH, Insall RH, Machesky LM (2017) Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin. Curr Biol 27(5):624–637. doi:10.1016/j.cub.2017.01.033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Riechelmann R, Grothey A (2017) Antiangiogenic therapy for refractory colorectal cancer: current options and future strategies. Ther Adv Med Oncol 9(2):106–126. doi:10.1177/1758834016676703

    Article  PubMed  Google Scholar 

  26. Ribatti D (2017) Epithelial-mesenchymal transition in morphogenesis, cancer progression and angiogenesis. Exp Cell Res 353(1):1–5. doi:10.1016/j.yexcr.2017.02.041

    Article  CAS  PubMed  Google Scholar 

  27. Corominas D, Vollmer I, Paredes P (2017) Pulmonary Tumor Embolism due to Cardiac Metastasis of Lung Cancer. Arch Bronconeumol. doi:10.1016/j.arbres.2017.01.008

    PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported in part by the Grants from The National Natural Science Foundation of China (81372304, 81572667, 81102065); the National “111” Project (Project #111-2-12); the Natural Science Foundation of Hunan Province, China (2015JJ2178); the Natural Science Foundation of Shandong Province, China (ZR2016HQ28); the Science and Technology Development Project of Jining ([2016] No. 56-28), and the Doctoral Fund of Affiliated Hospital of Jining Medical University (2016-BS-002).

Author information

Authors and Affiliations

  1. The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, 410078, Hunan, China

    Wei Wang, Junjun Li, Shengnan Chen, Jing Cai, Zhaoyang Zeng, Xiaoling Li, Wei Xiong, Guiyuan Li & Bo Xiang

  2. Department of Pathology, Affiliated Hospital of Jining Medical University, Jining, 272029, Shandong, China

    Wei Wang & Renya Zhang

  3. Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Mei Yi

  4. Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China

    Junjun Li, Shengnan Chen, Jing Cai, Zhaoyang Zeng, Xiaoling Li, Wei Xiong, Guiyuan Li & Bo Xiang

  5. Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China

    Li Wang

Authors
  1. Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mei Yi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Renya Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Junjun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shengnan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jing Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhaoyang Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiaoling Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wei Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Li Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Guiyuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Bo Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bo Xiang.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, W., Yi, M., Zhang, R. et al. Vimentin is a crucial target for anti-metastasis therapy of nasopharyngeal carcinoma. Mol Cell Biochem 438, 47–57 (2018). https://doi.org/10.1007/s11010-017-3112-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-017-3112-z

Keywords

Search

Navigation