VEGFR2 Expression in Head and Neck Squamous Cell Carcinoma Cancer Cells Mediates Proliferation and Invasion

  • Xu, Hui-Min (Department of Otolaryngology-Head and Neck Surgery, Changshu No.1 People's Hospital Affiliated to Soochow University) ;
  • Zhu, Jian-Guo (Department of Otolaryngology-Head and Neck Surgery, Changshu No.1 People's Hospital Affiliated to Soochow University) ;
  • Gu, Lian (Department of Otolaryngology-Head and Neck Surgery, Changshu No.1 People's Hospital Affiliated to Soochow University) ;
  • Hu, Song-Qun (Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Nantong University) ;
  • Wu, Hao (Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Nantong University)
  • Published : 2016.06.01


Vascular endothelial growth factor 2 (VEGFR2) was initially identified as a receptor of VEGF on endothelial cells with a role in regulating angiogenesis during organism development and tumorigenesis. Previously, in cancer tissue, VEGFR2 has been reported to be expressed in endothelial cells. In our research, we found that VEGFR2 was expressed not only in endothelial cells but also cancer cells in head and neck squamous cell carcinomas (HNSCCs). Knockdown of VEGFR2 in Hep2 cells could arrest the cell cycle in G0/G1, leading to a decrease in proliferation. We also present evidence that MAPK/ERK signal pathways and expression of CDK1 downstream of VEGFR2 might regulate proliferation and cell cycle arrest. Furthermore, we discovered that down-regulate VEGRF2 in Hep2 cells could significantly affect the invasion ability. Taken together, our data suggest that VEGFR2 might regulate proliferation and invasion in HNSCC cancer cells in vivo.




  1. Beck B, Driessens G, Goossens S, et al (2011). A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumours. Nature, 478, 399-403.
  2. Bergers G, Benjamin LE (2003). Tumorigenesis and the angiogenic switch. Nat Rev Cancer, 3, 401-10.
  3. Brekken RA, Thorpe PE (2001). Vascular endothelial growth factor and vascular targeting of solid tumors. Anticancer Res, 21, 4221-9.
  4. Cheng GZ, Zhang W, Wang LH (2008). Regulation of cancer cell survival, migration, and invasion by Twist: AKT2 comes to interplay. Cancer Res, 68, 957-60.
  5. Corlu A, Loyer P (2012). Regulation of the g1/s transition in hepatocytes: involvement of the cyclin-dependent kinase cdk1 in the DNA replication. Int J Hepatol, 2012, 689324.
  6. Croci DO, Rabinovich GA (2014). Linking tumor hypoxia with VEGFR2 signaling and compensatory angiogenesis: Glycans make the difference. Oncoimmunol, 3, 29380.
  7. Das LC, Karrison TG, Witt ME, et al (2014). Comparison of outcomes of locoregionally advanced oropharyngeal and non-oropharyngeal squamous cell carcinoma over two decades. Ann Oncol.
  8. Folkman J, Shing Y (1992). Angiogenesis. J Biol Chem, 267, 10931-4.
  9. Gasparini G, Longo R, Toi M, et al (2005). Angiogenic inhibitors: a new therapeutic strategy in oncology. Nat Clin Pract Oncol, 2, 562-77.
  10. Guo S, Colbert LS, Fuller M, et al (2010). Vascular endothelial growth factor receptor-2 in breast cancer. Biochim Biophys Acta, 1806, 108-21.
  11. Inglehart RC, Scanlon CS, D'Silva NJ (2014). Reviewing and reconsidering invasion assays in head and neck cancer. Oral Oncol, 50, 1137-43.
  12. Kauppila JH, Korvala J, Siirila K, et al (2014). Toll-like receptor 9 mediates invasion and predicts prognosis in squamous cell carcinoma of the mobile tongue. J Oral Pathol Med.
  13. Kontic M, Milovanovic J, Colovic Z, et al (2014). Epidermal growth factor receptor (EGFR) expression in patients with laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol.
  14. Krajewska J, Handkiewicz-Junak D, Jarzab B (2015). Sorafenib for the treatment of thyroid cancer: an updated review. Expert Opin Pharmacother, 1-11.
  15. Lichtenberger BM, Tan PK, Niederleithner H, et al (2010). Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote epithelial cancer development. Cell, 140, 268-79.
  16. Mokhtari S (2012). Mechanisms of cyst formation in metastatic lymph nodes of head and neck squamous cell carcinoma. Diagn Pathol, 7, 6.
  17. Parast CV, Mroczkowski B, Pinko C, et al (1998). Characterization and kinetic mechanism of catalytic domain of human vascular endothelial growth factor receptor-2 tyrosine kinase (VEGFR2 TK), a key enzyme in angiogenesis. Biochemistry, 37, 16788-801.
  18. Pathare SM, Gerstung M, Beerenwinkel N, et al (2011). Clinicopathological and prognostic implications of genetic alterations in oral cancers. Oncol Lett, 2, 445-51.
  19. Rehman AO, Wang CY (2009). CXCL12/SDF-1 alpha activates NF-kappaB and promotes oral cancer invasion through the Carma3/Bcl10/Malt1 complex. Int J Oral Sci, 1, 105-18.
  20. Reya T, Clevers H (2005). Wnt signalling in stem cells and cancer. Nature, 434, 843-50.
  21. Rothenberg SM, Ellisen LW (2012). The molecular pathogenesis of head and neck squamous cell carcinoma. J Clin Invest, 122, 1951-7.
  22. Schulze WX, Deng L, Mann M (2005). Phosphotyrosine interactome of the ErbB-receptor kinase family. Mol Syst Biol, 1, 2005-8.
  23. Segiet OA, Michalski M, Brzozowa-Zasada M, et al (2015). Angiogenesis in primary hyperparathyroidism. Ann Diagn Pathol.
  24. Silva SR, Bowen KA, Rychahou PG, et al (2011). VEGFR-2 expression in carcinoid cancer cells and its role in tumor growth and metastasis. Int J Cancer, 128, 1045-56.
  25. Xuan ZX, Li LN, Zhang Q, et al (2014). Fully human VEGFR2 monoclonal antibody BC001 attenuates tumor angiogenesis and inhibits tumor growth. Int J Oncol, 45, 2411-20.
  26. Ye F, Chen HZ, Xie X, et al (2004). Vascular endothelial growth factor (VEGF) and ovarian carcinoma cell supernatant activate signal transducers and activators of transcription (STATs) via VEGF receptor-2 (KDR) in human hemopoietic progenitor cells. Gynecol Oncol, 94, 125-33.

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