TIPE1 suppresses invasion and migration through down‐regulating Wnt/β‐catenin pathway in gastric cancer |
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| Authors: | Wenwen Liu Ye Chen Hua Xie Yongmin Guo Dandan Ren Yupeng Li Xu Jing Dongliang Li Xiao Wang Miaoqing Zhao Tianfeng Zhu Ziying Wang Xinbing Wei Fei Gao Xiaojie Wang Suxia Liu Yan Zhang Fan Yi |
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| Affiliation: | 1. Department of Pharmacology, Shandong University School of Medicine, Jinan, China;2. Taishan District Center for Disease Control and Prevention, Taian, China;3. Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China;4. Department of Pediatrics, Peoples Hospital of Rizhao, Rizhao, China;5. Department of Pathology, Shandong University School of Medicine, Jinan, China;6. Department of Pathology, Shandong Provincial Hospital, Shandong University, Jinan, China;7. Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China;8. Department of Immunology, Shandong University School of Medicine, Jinan, China |
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| Abstract: | Epithelial–mesenchymal transition (EMT) plays an important role in the invasiveness and metastasis of gastric cancer. Therefore, identifying key molecules involved in EMT will provide new therapeutic strategy for treating patients with gastric cancer. TIPE1 is a newly identified member of the TIPE (TNFAIP8) family, and its contributions to progression and metastasis have not been evaluated. In this study, we found that the levels of TIPE1 were significantly reduced and inversely correlated with differentiation status and distant metastasis in primary gastric cancer tissues. We further observed overexpression of TIPE1 in aggressive gastric cancer cell lines decreased their metastatic properties both in vitro and in vivo as demonstrated by markedly inhibiting EMT and metastasis of gastric cancer cells in nude mice. Consistently, gene silencing of TIPE1 in well‐differentiated gastric cancer cell line (AGS) inhibited these processes. Mechanistically, we found that TIPE1‐medicated Wnt/β‐catenin signalling was one of the critical signal transduction pathways that link TIPE1 to EMT inhibition. Importantly, TIPE1 dramatically restrained the expression and activities of MMP2 and MMP9 which are demonstrated to promote tumour progression and are implicated in EMT. Collectively, these findings provide new evidence for a better understanding of the biological activities of TIPE1 in progression and metastasis of gastric cancer and suggest that TIPE1 may be an innovative diagnostic and therapeutic target of gastric cancer. |
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| Keywords: | TIPE1 gastric cancer epithelial– mesenchymal transition Wnt/β ‐catenin pathway |
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