Role of EGFL7/EGFR-signaling pathway in migration and invasion of growth hormone-producing pituitary adenomas.

Abstract	Currently, the primary therapeutic strategy for most growth hormone-producing pituitary adenomas (GHPA) is surgery. Due to the invasiveness of GHPA, high recurrence has limited the benefit of complete adenoma removal surgery. Epidermal growth factor-like domain 7 (EGFL7) is a secreted factor implicated in tumor angiogenesis, growth, invasiveness and metastasis in GHPA. Herein, we observed that the expression level of EGFL7 and p-EGFR in invasive GHPA was much higher than that of non-invasive GHPA. The overexpression of EGFL7 was positively correlated with activation of EGFR (p-EGFR). Noticeably, EGFL7 knockdown significantly inhibited activation of EGFR signaling cascades, including p-ERGR, p-AKT and p-ERK. Further studies showed that EGFL7 knockdown or pharmacological inhibition of EGFR-pathway, using EGFR inhibitor Tyrphostin AG-1478, significantly suppressed migration and invasion of GH3 and GT1-1 cells. In summary, our findings suggest that EGFL7 is a key factor for regulation of EGFR signaling pathway and plays an important role in migration and invasion of invasive GHPA.
Authors	Qian Liu, Junwen Zhang, Hua Gao, Taoyang Yuan, Jie Kang, Lu Jin, Songbai Gui, Yazhuo Zhang
Journal	Science China. Life sciences (Sci China Life Sci) Vol. 61 Issue 8 Pg. 893-901 (08 2018) ISSN: 1869-1889 [Electronic] China
PMID	29951953 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Calcium-Binding Proteins EGF Family of Proteins EGFL7 protein, human Endothelial Growth Factors Enzyme Inhibitors Quinazolines Tyrphostins RTKI cpd ErbB Receptors
Topics	Adenoma (genetics, metabolism, pathology) Animals Calcium-Binding Proteins Cell Line, Tumor Cell Movement EGF Family of Proteins Endothelial Growth Factors (genetics, metabolism) Enzyme Inhibitors (pharmacology) ErbB Receptors (antagonists & inhibitors, genetics, metabolism) Growth Hormone-Secreting Pituitary Adenoma (genetics, metabolism, pathology) Humans Mice Neoplasm Invasiveness Quinazolines (pharmacology) RNA Interference Rats Signal Transduction (drug effects) Tyrphostins (pharmacology)

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