Vimentin is a crucial target for anti-metastasis therapy of nasopharyngeal carcinoma
- 363 Downloads
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.
KeywordsVimentin Metastasis Tumor plaque Nasopharyngeal carcinoma
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 ( No. 56-28), and the Doctoral Fund of Affiliated Hospital of Jining Medical University (2016-BS-002).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- 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 CrossRefPubMedPubMedCentralGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedPubMedCentralGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedPubMedCentralGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedPubMedCentralGoogle 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 CrossRefPubMedPubMedCentralGoogle 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 CrossRefPubMedPubMedCentralGoogle Scholar