Inhibition of epidermal growth factor receptor signaling prohibits metastasis of gastric cancer via downregulation of MMP7 and MMP13

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• 作者：Yinghai Ye (1)
  Xiaocong Zhou (1)
  Xiaoyang Li (1)
  Yinhe Tang (2)
  Yusheng Sun (3)
  Jun Fang (3)
  
• 关键词：Gastric cancer ; Epidermal growth factor receptor ; PI3K ; Akt ; ERK/MAPK ; MMP7 ; MMP13
• 刊名：Tumor Biology
• 出版年：2014
• 出版时间：November 2014
• 年：2014
• 卷：35
• 期：11
• 页码：10891-10896
• 全文大小：357 KB
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• 作者单位：Yinghai Ye (1)
  Xiaocong Zhou (1)
  Xiaoyang Li (1)
  Yinhe Tang (2)
  Yusheng Sun (3)
  Jun Fang (3)
  
  1. Department of Surgery, Wenzhou Central Hospital, Wenzhou, China
  2. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
  3. Department of Trauma Surgery, The First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Lane, Wenzhou, 32500, China
  
• ISSN：1423-0380

文摘

The molecular pathway regulating gastric carcinoma (GC) invasiveness and metastasis remains elusive. Here, we detected significant increase in the phosphorylated epidermal growth factor receptor (pEGFR), MMP7, and MMP13 in the resected GC, compared with the adjacent normal tissue, in patients. Moreover, strong positive correlation was detected between pEGFR and MMP7, and between pEGFR and MMP13 in GC. To examine whether a causal link exists, we used two human GC lines, SNU-5 and AGS, to study the cross talk between EGFR signaling activation, and expression of MMP7 and MMP13. We found that EGF-induced EGFR phosphorylation activated both MMP7 and MMP13, and consequently cancer invasiveness. EGF-induced activation of MMP7 and MMP13 can be both inhibited by use of an inhibitor for EGFR. EGF-induced activation of MMP7 can be also significantly inhibited by use of an inhibitor for Akt, but not an inhibitor for ERK1/2, while EGF-induced activation of MMP13 can be significantly inhibited by use of an inhibitor for ERK1/2, but not by an inhibitor for Akt. These data suggest that EGF-induced activation of MMP7 and MMP13 in GC is through phosphatidylinositol 3-kinase (PI3K) and extracellular-related kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway, respectively. Our study thus highlights EGFR signaling regulated MMP7 and MMP13 activation as molecular basis for metastasis of GC, and further demonstrate that different signaling pathway cascades are involved in the downstream signaling transduction.