EphA3 contributes to tumor growth and angiogenesis in human gastric cancer cells

Lv,Xiao‑Ye; Wang,Jian; Huang,Fang; Wang,Peng; Zhou,Jian‑Guang; Wei,Bo; Li,Shan‑Hu

doi:10.3892/or.2018.6586

EphA3 contributes to tumor growth and angiogenesis in human gastric cancer cells

Authors:
- Xiao‑Ye Lv
- Jian Wang
- Fang Huang
- Peng Wang
- Jian‑Guang Zhou
- Bo Wei
- Shan‑Hu Li
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Affiliations: Department of Cell Engineering, Beijing Institute of Biotechnology, Beijing 100850, P.R. China, Department of General Surgery, The General Hospital of People's Liberation Army, Beijing 100853, P.R. China
Published online on: July 20, 2018 https://doi.org/10.3892/or.2018.6586
Pages: 2408-2416

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Abstract

Eph receptor tyrosine kinases and their ephrin ligands, mediate an important cell communication system both in normal and oncogenic development, and play central roles in a series of processes including angiogenesis, stem cell maintenance and cancer metastasis. Eph receptor A3 (EphA3), commonly overexpressed in a broad range of cancers, including gastric cancer (GC), is related to tumor progression. Our previous study revealed that EphA3 may play important roles in tumorigenesis and angiogenesis in GC. However, its exact role and the mechanisms underlying its function in GC remain unclear. In the present study, lentivirus‑mediated RNA interference was employed to knock down the expression of EphA3 in GC HGC‑27 cells. Functional analyses indicated that depletion of EphA3 expression inhibited the cell growth and tumorigenicity of HGC‑27 cells in vitro and in vivo. Furthermore, knockdown of the expression of EphA3 in HGC‑27 cells inhibited tube formation and migration of HUVEC endothelial cells. Tumor angiogenesis in vivo was also inhibited upon EphA3 knockdown in HGC‑27 cells, with reduced microvessel density (MVD) in xenograft models. We further revealed that EphA3 depletion inhibited tumor angiogenesis and migration through the signal transducer and activator of transcription 3/vascular endothelial growth factor (STAT3/VEGF) signaling pathway. These results indicated that EphA3 may be an effective prognostic indicator and a potential target for GC therapy.

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