Correlation between HGF/c-Met and Notch1 signaling pathways in human gastric cancer cells

Kuo Hung Huang, I. Cheng Sung, Wen Liang Fang, Chin Wen Chi, Tien Shun Yeh, Hsin Chen Lee, Pen Hui Yin, Anna Fen Yau Li, Chew Wun Wu, Yi Ming Shyr, Muh Hwa Yang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


In recent decades, research concerning gastric carcinogenesis has rapidly progressed. It is evident that hepatocyte growth factor (HGF) is clinically related to gastric cancer progression and metastasis. In addition, previous studies have found that expression of Notch ligand Jagged1 is correlated with the poor prognosis of gastric cancer. However, the interaction between the HGF/c-Met and Notch1 signaling pathways remains unknown. In the present study, we found that gastric cancer patients with positive c-Met expression exhibited poorer overall survival than patients without c-Met expression (P=0.043) and that Jagged1 expression was signifcantly correlated with c-Met expression (r=0.301; P=0.004) in human gastric cancer specimens. In addition, Jagged1 activity increased after HGF stimulation, which in turn increased the downstream expression of cyclooxygenase 2 (COX-2) in a timedependent manner. After knockdown of Notch1 intracellular domain (N1IC), HGF was found to increase the proliferation and migration ability in human gastric cancer cells. However, overexpression of N1IC still had no effect after HGF stimulation. Our study found a feedback loop between HGF/c-Met and Jagged1/Notch1 signaling. Furthermore, both HGF/c-Met and Notch1 signaling triggered COX-2 activity. These results suggest that gastric cancer progression is not associated with a unique signaling pathway and that a feedback loop may exist between the HGF/c-Met and Notch1 signaling pathways, which may result in therapeutic resistance. Therefore, multi-modality therapies should be considered for treating gastric cancer.

Original languageEnglish
Pages (from-to)294-302
Number of pages9
JournalOncology Reports
Issue number1
StatePublished - Jul 2018


  • Gastric cancer
  • Hepatocyte growth factor
  • HGF/c-Met
  • Jagged1
  • Notch pathway


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