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EN2 as an oncogene promotes tumor progression via regulating CCL20 in colorectal cancer
Yimin Li1, Jiaxin Liu1, Qing Xiao1
1Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China.
Abstract:
Engrailed-2 (EN2), a member of the engrailed homeobox family, has been shown to be abnormally expressed in a variety of cancers. However, the expression and the clinical significance of EN2 in colorectal cancer (CRC) are largely unknown. Firstly, we found that EN2 acted as an oncogene in CRC. EN2 was upregulated in colorectal cancer tissues compared with adjacent normal tissues. Higher EN2 expression was significantly associated with poorer survival rate. Knockdown of EN2 markedly inhibited proliferation and migration capacities of SW480 cells in vitro, and suppressed tumorigenicity in vivo. Mechanistically, Chemokine ligand 20 (CCL20), a member of the C-C motif chemokine subfamily, was identified as a direct target gene of EN2 in CRC. CCL20 expression was positively correlated with EN2 expression in CRC tissues. Moreover, EN2 promoted the proliferation and migration of CRC cells by regulating the expression of CCL20 in vitro. These results suggest that EN2 plays a critical role in the CRC tumor progression and may serve as a potential target for CRC prevention and therapy.
Insights
Engrailed-2 (EN2) acts as an oncogene in colorectal cancer (CRC), promoting tumor progression. Targeting EN2 and its downstream target, Chemokine ligand 20 (CCL20), may offer new therapeutic strategies for CRC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Engrailed-2 (EN2) is implicated in various cancers, but its role in colorectal cancer (CRC) remains unclear.
- Understanding EN2's function in CRC is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the expression and clinical significance of EN2 in colorectal cancer.
- To elucidate the underlying mechanisms of EN2's role in CRC progression.
Main Methods:
- Quantitative analysis of EN2 expression in CRC tissues versus normal tissues.
- In vitro cell proliferation and migration assays following EN2 knockdown.
- In vivo tumorigenicity studies.
- Identification and validation of EN2's direct target genes using molecular techniques.
Main Results:
- EN2 was significantly upregulated in CRC tissues and associated with poorer patient survival.
- EN2 knockdown inhibited CRC cell proliferation, migration, and in vivo tumor growth.
- Chemokine ligand 20 (CCL20) was identified as a direct downstream target of EN2.
- EN2 promoted CRC cell proliferation and migration by regulating CCL20 expression.
Conclusions:
- EN2 functions as an oncogene in colorectal cancer progression.
- EN2 and its target CCL20 represent potential therapeutic targets for CRC treatment and prevention.
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