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

Ziyu Zhu,Lili Bao,Haosheng Ni,Bingyue Duan,Yiwen You,Si Shi,Bo You,Ying Shan

doi:10.1002/cam4.1883

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.

Highlights

Nasopharyngeal carcinoma (NPC) is a squamous epithelial cell carcinoma with an incidence of 15‐50 cases per 100 000 and is especially prevalent in Southeast Asia.[1,2] Currently, with the application of intensity‐modulated radiotherapy, the locoregional control rate of nasopharyngeal carcinoma (NPC) is much higher than before.[3]
We found Epidermal growth factor‐like domain multiple 6 (EGFL6) was upregulated in NPC clinical samples tissues, blood serum (Figure 1A‐C), and cell lines (Figure 2A)
Our findings suggested that EGFL6 could promote the migration and proliferation of NPC cells in vitro and vivo

Summary

| INTRODUCTION

Nasopharyngeal carcinoma (NPC) is a squamous epithelial cell carcinoma with an incidence of 15‐50 cases per 100 000 and is especially prevalent in Southeast Asia.[1,2] Currently, with the application of intensity‐modulated radiotherapy, the locoregional control rate of NPC is much higher than before.[3]. Epidermal growth factor‐like domain multiple 6 (EGFL6) is an extracellular matrix protein, belongs to EGFL family and plays an important role in promoting the migration and angiogenesis of endothelial cells.[5,6] Recently, it is reported that EGFL6 regulates the metastasis of ALDH+ ovarian cancer cells and is overexpression in benign meningioma and oral squamous cell carcinoma.[5,7,8] EGFL6 implicates in the pathogenesis of benign meningioma via activating AKT pathway.[9] there is some lack of The metastatic ability of NPC was evaluated via counting the cell mass in zebrafish model

| MATERIALS AND METHODS

| RESULTS

| DISCUSSION