Synaptotagmin 1 Suppresses Colorectal Cancer Metastasis by Inhibiting ERK/MAPK Signaling-Mediated Tumor Cell Pseudopodial Formation and Migration
Author:
Shi Jianyun1, Li Wenjing1, Jia Zhenhua1, Peng Ying1, Hou Jiayi2, Li Ning3, Meng Ruijuan4, Fu Wei4ORCID, Feng Yanlin1ORCID, Wu Lifei1, Zhou Lan1, Wang Deping1, Shen Jing1, Chang Jiasong1, Wang Yanqiang5ORCID, Cao Jimin1
Affiliation:
1. Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan 030606, China 2. Department of Clinical Laboratory, Shanxi Provincial Academy of Traditional Chinese Medicine, Taiyuan 030071, China 3. Department of Gastrointestinal and Pancreatic Surgery & Hernia and Abdominal Surgery, Shanxi Provincial People’s Hospital, Taiyuan 030045, China 4. Department of Radiology, The First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan 030606, China 5. Translational Medicine Research Center, Shanxi Medical University, Taiyuan 030606, China
Abstract
Although synaptotagmin 1 (SYT1) has been identified participating in a variety of cancers, its role in colorectal cancer (CRC) remains an enigma. This study aimed to demonstrate the effect of SYT1 on CRC metastasis and the underlying mechanism. We first found that SYT1 expressions in CRC tissues were lower than in normal colorectal tissues from the CRC database and collected CRC patients. In addition to this, SYT1 expression was also lower in CRC cell lines than in the normal colorectal cell line. SYT1 expression was downregulated by TGF-β (an EMT mediator) in CRC cell lines. In vitro, SYT1 overexpression repressed pseudopodial formation and reduced cell migration and invasion of CRC cells. SYT1 overexpression also suppressed CRC metastasis in tumor-bearing nude mice in vivo. Moreover, SYT1 overexpression promoted the dephosphorylation of ERK1/2 and downregulated the expressions of Slug and Vimentin, two proteins tightly associated with EMT in tumor metastasis. In conclusion, SYT1 expression is downregulated in CRC. Overexpression of SYT1 suppresses CRC cell migration, invasion, and metastasis by inhibiting ERK/MAPK signaling-mediated CRC cell pseudopodial formation. The study suggests that SYT1 is a suppressor of CRC and may have the potential to be a therapeutic target for CRC.
Funder
Shanxi Province Science Foundation for Youths National Natural Science Foundation of China Shanxi “1331” Project Quality and Efficiency Improvement Plan Shanxi Medical University of Shanxi Province in China
Subject
Cancer Research,Oncology
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