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Epidermal growth factor-like domain multiple 6 (EGFL6) promotes the migration and invasion of gastric cancer cells by inducing epithelial-mesenchymal transition

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Summary

Epidermal growth factor-like domain multiple 6 (EGFL6) is implicated in tumor growth, metastasis and angiogenesis, and its ectopic alteration has been detected in aggressive malignancies. However, the pathophysiologic roles and molecular mechanisms of EGFL6 in gastric cancer (GC) remain to be elucidated. In this study, we investigated EGFL6 expression in GC cell lines and tissues using western blotting and immunohistochemistry. We found that EGFL6 was elevated expression in GC cell lines and tissues. The high expression of EGFL6 significantly was correlated with histological grade, depth of invasion, lymph node involvement, distant metastasis and TNM stage in GC and predicted poorer prognosis, and it could act an independent prognostic factor for GC patients. EGFL6 enhanced the proliferation, migration and invasion of GC cells. In addition, we identified the possible molecular mechanisms of EGFL6-involved epithelial-mesenchymal transition (EMT). EGFL6 regulated EMT process and induced metastasis partly through FAK/PI3K/AKT/mTOR, Notch and MAPK signaling pathways. In conclusion, EGFL6 confers an oncogenic function in GC progression and may be proposed as a potential therapeutic target for GC.

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Author notes

  1. Fu-Chun Huo, Wen-Tao Zhu and Xu Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Xuzhou Medical University, 209 Tong-shan Road, Xuzhou, 221004, Jiangsu, China

    Fu-Chun Huo, Wen-Tao Zhu & Jie Mou

  2. Department of general surgery, Xuzhou Children’s Hospital, Xuzhou Medical University, Quan shan District, Xuzhou, 221000, Jiangsu, China

    Xu Liu

  3. Department of Radiation Oncology, Xuzhou Central Hospital, Xuzhou, 221000, Jiangsu, China

    Yun Zhou

  4. Department of Oncological Radiotherapy, the Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China

    Lan-Sheng Zhang

  5. School of Pharmacy, Xuzhou Medical University, 209 Tong-shan Road, Xuzhou, 221004, Jiangsu, China

    Jie Mou

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  1. Fu-Chun Huo
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Correspondence to Lan-Sheng Zhang or Jie Mou.

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Experiments involved in GC tissues was approved by the Medical Ethics Committee of the Affiliated Hospital of Xuzhou Medical University. Animal experiments were performed in accordance with the Institutional Animal Care and Use Committee of Xuzhou Medical University.

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Huo, FC., Zhu, WT., Liu, X. et al. Epidermal growth factor-like domain multiple 6 (EGFL6) promotes the migration and invasion of gastric cancer cells by inducing epithelial-mesenchymal transition. Invest New Drugs 39, 304–316 (2021). https://doi.org/10.1007/s10637-020-01004-2

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