Journal
INVESTIGATIONAL NEW DRUGS
Volume 39, Issue 2, Pages 304-316Publisher
SPRINGER
DOI: 10.1007/s10637-020-01004-2
Keywords
EGFL6; Gastric cancer; Metastasis; Epithelial-mesenchymal transition
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EGFL6 is overexpressed in gastric cancer and associated with poor prognostic factors. It enhances cancer cell proliferation, migration, and invasion through regulating multiple signaling pathways. EGFL6 may serve as a potential therapeutic target for gastric cancer.
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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