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TES inhibits colorectal cancer progression through activation of p38
Huili Li1, Kun Huang2, Lu Gao3
1Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Abstract:
The human TESTIN (TES) gene has been identified as a candidate tumor suppressor based on its location at a common fragile site - a region where loss of heterozygosity has been detected in numerous types of tumors. To investigate its role in colorectal cancer (CRC), we examined TES protein levels in CRC tissue samples and cell lines. We observed that TES was markedly reduced in both CRC tissue and cell lines. Additionally, overexpression of TES significantly inhibited cell proliferation, migration, and invasion, while increasing cell apoptosis in colon cancer cells. By contrast, shRNA-mediated TES knockdown elicited the opposite effects. TES inhibited the progression of CRC by up-regulating pro-apoptotic proteins, down-regulating anti-apoptotic proteins, and simultaneously activating p38 mitogen-activated protein kinase (MAPK) signaling pathways. Collectively, these data indicate that TES functions as a necessary suppressor of CRC progression by activating p38-MAPK signaling pathways. This suggests that TES may have a potential application in CRC diagnosis and targeted gene therapy.
Insights
The TESTIN (TES) gene suppresses colorectal cancer (CRC) progression by activating p38-MAPK pathways. Reduced TES levels promote CRC, suggesting TES as a potential therapeutic target for colon cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The TESTIN (TES) gene is a candidate tumor suppressor located at a common fragile site.
- Loss of heterozygosity at this site is observed in various tumors, prompting investigation into its role in colorectal cancer (CRC).
Purpose of the Study:
- To investigate the role of the TESTIN (TES) gene in colorectal cancer (CRC) progression.
- To determine the effect of TES protein levels on CRC cell behavior and signaling pathways.
Main Methods:
- Examined TES protein levels in CRC tissues and cell lines.
- Utilized gene overexpression and shRNA-mediated knockdown to assess TES function in colon cancer cells.
- Analyzed the impact of TES on apoptosis, proliferation, migration, invasion, and p38 MAPK signaling.
Main Results:
- TES protein levels were significantly reduced in CRC tissues and cell lines.
- Overexpression of TES inhibited CRC cell proliferation, migration, and invasion, while promoting apoptosis.
- TES knockdown produced opposite effects, increasing CRC progression.
- TES functions by up-regulating pro-apoptotic proteins, down-regulating anti-apoptotic proteins, and activating p38 MAPK signaling.
Conclusions:
- TESTIN (TES) acts as a crucial suppressor of colorectal cancer progression.
- TES exerts its tumor-suppressive function through the activation of p38-MAPK signaling pathways.
- TES holds potential for CRC diagnosis and targeted gene therapy.
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