Epidermal growth factor-like domain multiple 6 (EGFL6) promotes the migration and invasion of gastric cancer cells by in
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PRECLINICAL STUDIES
Epidermal growth factor-like domain multiple 6 (EGFL6) promotes the migration and invasion of gastric cancer cells by inducing epithelial-mesenchymal transition Fu-Chun Huo 1 & Wen-Tao Zhu 1 & Xu Liu 2 & Yun Zhou 3 & Lan-Sheng Zhang 4 & Jie Mou 1,5 Received: 6 August 2020 / Accepted: 13 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords EGFL6 . Gastric cancer . Metastasis . Epithelial-mesenchymal transition
Introduction
Fu-Chun Huo, Wen-Tao Zhu and Xu Liu contributed equally to this work. * Lan-Sheng Zhang [email protected] * Jie Mou [email protected] 1
Department of Pathology, Xuzhou Medical University, 209 Tong-shan Road, Xuzhou 221004, Jiangsu, China
2
Department of general surgery, Xuzhou Children’s Hospital, Xuzhou Medical University, Quan shan District, Xuzhou 221000, Jiangsu, China
3
Department of Radiation Oncology, Xuzhou Central Hospital, Xuzhou 221000, Jiangsu, China
4
Department of Oncological Radiotherapy, the Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu, China
5
School of Pharmacy, Xuzhou Medical University, 209 Tong-shan Road, Xuzhou 221004, Jiangsu, China
Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer-related mortality globally, with estimated 783,000 deaths in 2018 according the GLOBOCAN 2018 data [1]. The patients with GC are usually at advanced stage with metastasis when diagnosed [2]. Despite the early diagnosis and successful endoscopic mucosal resection or endoscopic submucosal dissection, the local recurrence rate of GC ranges from 2.8% to 12.5% [2, 3]. The 5-year survival rate of patients with early GC has exceeded 90%, while that of patients with advanced GC is less than 30% [4]. The metastasis of GC accounts for a major cause of recurrence a
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