Xiaojuan Luo1, Yuchen He1, Haosheng Tang1, Yiqu Cao1, Menghui Gao1, Baoan Liu1,2, Zhongliang Hu1,2. 1. Department of Pathology, Xiangya Hospital, Central South University 87 Xiangya Road, Changsha 410008, Hunan, China. 2. Department of Pathology, Basic Medical Institute, Central South University 172 Tongzi Road, Changsha 410013, Hunan, China.
Abstract
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) initiates a variety of signals that lead to the invasion and metastasis of gastric cancer. Though drugs targeting HER2 have been applied in clinical practice, drug resistance remains a big challenge. This study aimed to propose a new therapeutic target by exploring the regulating pathway of HER2. METHODS: Reverse transcription polymerase chain reaction (RT-PCR), western blot and immunohistochemistry staining were used respectively to detect the expression of HER2, Twist, E-cadherin and Fascin1 in both HER2 knockdown and overexpressed cell lines. Trans-well chamber assay and wound healing assay were used to detect the invasive ability of gastric cancer cells. The correlation between HER2 and Twist was analyzed based on specimens obtained from 118 patients with gastric cancer. RESULTS: HER2 silencing decreased the expression of Twist (P<0.05) and increased the expression of E-cadherin (P<0.05), while the expression of Fascin1 remained unchanged (P>0.05) and the migration and invasion abilities of cancer cells were weakened (P<0.01). On the contrary overexpression of HER2 increased the expression of Twist (P<0.05) and decreased the expression of E-cadherin (P<0.05), while the expression of Fascin1 still remained unchanged (P>0.05), and the migration and invasion abilities of cancer cells were enhanced (P<0.01). Our data indicated that the HER2 kinase domain was not involved in the regulation of Twist or E-cadherin. In addition, the expression of HER2 was positively correlated with the EMT-related transcription factor Twist in gastric cancer tissues. CONCLUSION: HER2 could promote the invasion and migration of gastric cancer cells by down-regulating E-cadherin and up-regulating Twist, which indicated that E-cadherin and Twist were both promising therapeutic targets. AJTR
BACKGROUND:Human epidermal growth factor receptor 2 (HER2) initiates a variety of signals that lead to the invasion and metastasis of gastric cancer. Though drugs targeting HER2 have been applied in clinical practice, drug resistance remains a big challenge. This study aimed to propose a new therapeutic target by exploring the regulating pathway of HER2. METHODS: Reverse transcription polymerase chain reaction (RT-PCR), western blot and immunohistochemistry staining were used respectively to detect the expression of HER2, Twist, E-cadherin and Fascin1 in both HER2 knockdown and overexpressed cell lines. Trans-well chamber assay and wound healing assay were used to detect the invasive ability of gastric cancer cells. The correlation between HER2 and Twist was analyzed based on specimens obtained from 118 patients with gastric cancer. RESULTS:HER2 silencing decreased the expression of Twist (P<0.05) and increased the expression of E-cadherin (P<0.05), while the expression of Fascin1 remained unchanged (P>0.05) and the migration and invasion abilities of cancer cells were weakened (P<0.01). On the contrary overexpression of HER2 increased the expression of Twist (P<0.05) and decreased the expression of E-cadherin (P<0.05), while the expression of Fascin1 still remained unchanged (P>0.05), and the migration and invasion abilities of cancer cells were enhanced (P<0.01). Our data indicated that the HER2 kinase domain was not involved in the regulation of Twist or E-cadherin. In addition, the expression of HER2 was positively correlated with the EMT-related transcription factor Twist in gastric cancer tissues. CONCLUSION:HER2 could promote the invasion and migration of gastric cancer cells by down-regulating E-cadherin and up-regulating Twist, which indicated that E-cadherin and Twist were both promising therapeutic targets. AJTR