Elevated EGFL6 modulates cell metastasis and growth via AKT pathway in nasopharyngeal carcinoma

Cancer Med. 2018 Dec;7(12):6281-6289. doi: 10.1002/cam4.1883. Epub 2018 Nov 15.

Abstract

Epidermal growth factor-like domain multiple 6 (EGFL6) is a secreted protein, regulates maintenance and metastasis of cancer cells. Nevertheless, how EGFL6 participates in the progression and tumorigenesis of nasopharyngeal carcinoma (NPC) remains unclear. In our study, EGFL6 was detected highly expressed in 20 NPC tissues compared with normal tissues by IHC assay. Then, the level of EGFL6 in NPC serum and NPC cells was explored through enzyme-linked immunosorbent assay and western blot, the results consistent with IHC. More interestingly, EGFL6 accelerated the migration and growth of NPC in vitro assays. Considering the mechanism of migration, NPC cells were cultured with AKT activator, revealing EGFL6 facilitated the progression of NPC via AKT. Moreover, the same effect of EGFL6 in promoting NPC growth was proved in nude mice. Furthermore, heat-shock zebrafish model was established with EGFL6 overexpression. Then, CNE2 cells were injected into the model and cells mass was observed, showing that EGFL6 enhanced the migration and metastasis of NPC. Currently, as the prognosis of NPC is severely affected by distant metastasis, it might be a new therapeutic target toward EGFL6. Taken together, our results suggested that EGFL6 acts as a potential positive regulator in the migration and proliferation of NPC.

Keywords: AKT; EGFL6; growth; metastasis; nasopharyngeal carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Binding Proteins
  • Cell Adhesion Molecules
  • Cell Line, Tumor
  • Cell Movement
  • Humans
  • Membrane Glycoproteins / metabolism*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nasopharyngeal Carcinoma / metabolism*
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction
  • Zebrafish

Substances

  • Calcium-Binding Proteins
  • Cell Adhesion Molecules
  • EGFL6 protein, human
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-akt