Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100500, China.
Key Laboratory of Central Nervous System Injury Research, Beijing Institute for Brain Disorders Brain Tumor Center, China National Clinical Research Center for Neurological Diseases, Capital Medical University, Beijing, 100050, China.
Sci China Life Sci. 2018 Aug;61(8):893-901. doi: 10.1007/s11427-018-9320-4. Epub 2018 Jun 26.
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.
目前，大多数生长激素分泌型垂体腺瘤（GHPA）的主要治疗策略是手术。由于 GHPA 的侵袭性，高复发率限制了完全腺瘤切除术的获益。表皮生长因子样结构域 7（EGFL7）是一种分泌因子，与 GHPA 的肿瘤血管生成、生长、侵袭和转移有关。在此，我们观察到 EGFL7 和 p-EGFR 在侵袭性 GHPA 中的表达水平明显高于非侵袭性 GHPA。EGFL7 的过表达与 EGFR（p-EGFR）的激活呈正相关。值得注意的是，EGFL7 敲低显著抑制了 EGFR 信号级联的激活，包括 p-ERGR、p-AKT 和 p-ERK。进一步的研究表明，EGFL7 敲低或 EGFR 通路的药理学抑制，使用 EGFR 抑制剂 Tyrphostin AG-1478，显著抑制了 GH3 和 GT1-1 细胞的迁移和侵袭。综上所述，我们的研究结果表明，EGFL7 是调节 EGFR 信号通路的关键因素，在侵袭性 GHPA 的迁移和侵袭中发挥重要作用。
