Bidirectional regulation between TMEFF2 and STAT3 may contribute to Helicobacter pylori-associated gastric carcinogenesis
Correction(s) for this article
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Erratum
- Volume 138Issue 1International Journal of Cancer
- pages: E2-E2
- First Published online: October 15, 2015
Tian-Tian Sun
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001 China
T.-T.S. and J.-Y.T. contributed equally to this work.
Search for more papers by this authorJia-Yin Tang
Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001 China
State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai, China
Department of General Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
T.-T.S. and J.-Y.T. contributed equally to this work.
Search for more papers by this authorWan Du
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001 China
Search for more papers by this authorHui-Jun Zhao
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001 China
Search for more papers by this authorGang Zhao
Department of General Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Search for more papers by this authorSheng-Li Yang
Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001 China
State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai, China
Search for more papers by this authorCorresponding Author
Hao-Yan Chen
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001 China
Correspondence to: Jing-Yuan Fang, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected] or Jie Hong, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected] or Hao-Yan Chen, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected]Search for more papers by this authorCorresponding Author
Jie Hong
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001 China
Correspondence to: Jing-Yuan Fang, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected] or Jie Hong, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected] or Hao-Yan Chen, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected]Search for more papers by this authorCorresponding Author
Jing-Yuan Fang
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001 China
Correspondence to: Jing-Yuan Fang, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected] or Jie Hong, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected] or Hao-Yan Chen, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected]Search for more papers by this authorTian-Tian Sun
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001 China
T.-T.S. and J.-Y.T. contributed equally to this work.
Search for more papers by this authorJia-Yin Tang
Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001 China
State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai, China
Department of General Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
T.-T.S. and J.-Y.T. contributed equally to this work.
Search for more papers by this authorWan Du
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001 China
Search for more papers by this authorHui-Jun Zhao
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001 China
Search for more papers by this authorGang Zhao
Department of General Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Search for more papers by this authorSheng-Li Yang
Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001 China
State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai, China
Search for more papers by this authorCorresponding Author
Hao-Yan Chen
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001 China
Correspondence to: Jing-Yuan Fang, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected] or Jie Hong, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected] or Hao-Yan Chen, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected]Search for more papers by this authorCorresponding Author
Jie Hong
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001 China
Correspondence to: Jing-Yuan Fang, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected] or Jie Hong, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected] or Hao-Yan Chen, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected]Search for more papers by this authorCorresponding Author
Jing-Yuan Fang
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001 China
Correspondence to: Jing-Yuan Fang, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected] or Jie Hong, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected] or Hao-Yan Chen, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Institute for Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China, Tel.: +0086-21-63200874, E-mail: [email protected]Search for more papers by this authorAbstract
The transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) is a single-pass transmembrane protein, and it is downregulated in human gastric cancer and levels correlate with tumor progression and time of survival. However, the mechanism of its dysregulation in gastric cancer is little known. Here we investigate its regulatory mechanism and the bidirectional regulation between TMEFF2 and STAT3 in gastric carcinogenesis. TMEFF2 expression was decreased after Helicobacter pylori (H. pylori) infection in vivo and in vitro. STAT3 directly binds to the promoter of TMEFF2 and regulates H. pylori-induced TMEFF2 downregulation in normal gastric GES-1 cells and gastric cancer AGS cells. Conversely, TMEFF2 may suppress the phosphorylation of STAT3 and TMEFF2-induced downregulation of STAT3 phosphorylation may depend on SHP-1. A highly inverse correlation between the expression of TMEFF2 and pSTAT3 was also revealed in gastric tissues. We now show the deregulation mechanism of TMEFF2 in gastric carcinogenesis and identify TMEFF2 as a new target gene of STAT3. The phosphorylation of STAT3 may be negatively regulated by TMEFF2, and the bidirectional regulation between TMEFF2 and STAT3 may contribute to H. pylori-associated gastric carcinogenesis.© 2014 UICC
Abstract
What's new?
Certain tumor suppressors and signaling pathways are dysregulated following infection with Helicobacter pylori, but the molecular mechanisms by which the bacterium induces gastric cancer are not fully understood. Here, expression of TMEFF2, a transmembrane protein previously implicated in human gastric cancer, was found to be decreased in response to H. pylori infection, an effect attributed to H. pylori activation of STAT3. Reduced expression of TMEFF2 was associated with elevated STAT3 phosphorylation. Negative regulation of STAT3 by TMEFF2 likely involves interaction with SHP-1. The findings suggest that bidirectional regulation between TMEFF2 and STAT3 contributes to H. pylori-associated gastric carcinogenesis.
Supporting Information
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