Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver Metastasis
Background. Cancer stem cells (CSCs) are involved in liver metastasis in colorectal cancer (CRC). Activin and hepatocyte growth factor (HGF) are important regulators of stem cell properties. This study was performed to explore the effect of activin and HGF on CRC invasion and metastasis. The key gen...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-01-01
|
| Series: | Canadian Journal of Gastroenterology and Hepatology |
| Online Access: | http://dx.doi.org/10.1155/2022/8996203 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832552720135880704 |
|---|---|
| author | Hong Peng Ting Ye Lei Deng Xiaofang Yang Zheng Jiang Jinjun Guo |
| author_facet | Hong Peng Ting Ye Lei Deng Xiaofang Yang Zheng Jiang Jinjun Guo |
| author_sort | Hong Peng |
| collection | DOAJ |
| description | Background. Cancer stem cells (CSCs) are involved in liver metastasis in colorectal cancer (CRC). Activin and hepatocyte growth factor (HGF) are important regulators of stem cell properties. This study was performed to explore the effect of activin and HGF on CRC invasion and metastasis. The key genes involved in the action of activin and HGF in CRC were identified. Methods. HCT116 CRC cells were sequentially treated with activin and HGF and examined for migration and invasion in vitro and liver metastasis in vivo. RNA sequencing was performed to identify differentially expressed genes in response to activin and HGF. Results. Sequential treatment with activin and HGF-enhanced CRC cell migration, invasion, and metastasis. CXCR4 and AFP expressions were increased by activin and HGF treatment. Knockdown of FOXM1 blocked liver metastasis from HCT116 cells pretreated with activin and HGF and suppressed CXCR4 and AFP expression. Activin alone increased the mRNA and protein expression of FOXM1. In contrast, HGF alone enhanced the phosphorylation of FOXM1, without altering the total protein level of FOXM1. SMAD2 was required for activin-mediated FOXM1 induction. FOXM1 transactivated CXCR4 by directly binding to the promoter of CXCR4. Additionally, CXCR4 regulated AFP expression through the NF-κB pathway. Conclusions. Sequential treatment with activin and HGF accelerates CRC invasion and liver metastasis, which involves the upregulation and activation of FOXM1 and induction of CXCR4 and AFP. |
| format | Article |
| id | doaj-art-7ea2cd40900443a5b06a0d97cacda86b |
| institution | Kabale University |
| issn | 2291-2797 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Canadian Journal of Gastroenterology and Hepatology |
| spelling | doaj-art-7ea2cd40900443a5b06a0d97cacda86b2025-02-03T05:57:59ZengWileyCanadian Journal of Gastroenterology and Hepatology2291-27972022-01-01202210.1155/2022/8996203Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver MetastasisHong Peng0Ting Ye1Lei Deng2Xiaofang Yang3Zheng Jiang4Jinjun Guo5Bishan Hospital of ChongqingChongqing Emergency Medical CenterChongqing Emergency Medical CenterChongqing Emergency Medical CenterDepartment of GastroenterologyBishan Hospital of ChongqingBackground. Cancer stem cells (CSCs) are involved in liver metastasis in colorectal cancer (CRC). Activin and hepatocyte growth factor (HGF) are important regulators of stem cell properties. This study was performed to explore the effect of activin and HGF on CRC invasion and metastasis. The key genes involved in the action of activin and HGF in CRC were identified. Methods. HCT116 CRC cells were sequentially treated with activin and HGF and examined for migration and invasion in vitro and liver metastasis in vivo. RNA sequencing was performed to identify differentially expressed genes in response to activin and HGF. Results. Sequential treatment with activin and HGF-enhanced CRC cell migration, invasion, and metastasis. CXCR4 and AFP expressions were increased by activin and HGF treatment. Knockdown of FOXM1 blocked liver metastasis from HCT116 cells pretreated with activin and HGF and suppressed CXCR4 and AFP expression. Activin alone increased the mRNA and protein expression of FOXM1. In contrast, HGF alone enhanced the phosphorylation of FOXM1, without altering the total protein level of FOXM1. SMAD2 was required for activin-mediated FOXM1 induction. FOXM1 transactivated CXCR4 by directly binding to the promoter of CXCR4. Additionally, CXCR4 regulated AFP expression through the NF-κB pathway. Conclusions. Sequential treatment with activin and HGF accelerates CRC invasion and liver metastasis, which involves the upregulation and activation of FOXM1 and induction of CXCR4 and AFP.http://dx.doi.org/10.1155/2022/8996203 |
| spellingShingle | Hong Peng Ting Ye Lei Deng Xiaofang Yang Zheng Jiang Jinjun Guo Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver Metastasis Canadian Journal of Gastroenterology and Hepatology |
| title | Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver Metastasis |
| title_full | Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver Metastasis |
| title_fullStr | Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver Metastasis |
| title_full_unstemmed | Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver Metastasis |
| title_short | Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver Metastasis |
| title_sort | sequential treatment with activin and hepatocyte growth factor induces foxm1 to promote colorectal cancer liver metastasis |
| url | http://dx.doi.org/10.1155/2022/8996203 |
| work_keys_str_mv | AT hongpeng sequentialtreatmentwithactivinandhepatocytegrowthfactorinducesfoxm1topromotecolorectalcancerlivermetastasis AT tingye sequentialtreatmentwithactivinandhepatocytegrowthfactorinducesfoxm1topromotecolorectalcancerlivermetastasis AT leideng sequentialtreatmentwithactivinandhepatocytegrowthfactorinducesfoxm1topromotecolorectalcancerlivermetastasis AT xiaofangyang sequentialtreatmentwithactivinandhepatocytegrowthfactorinducesfoxm1topromotecolorectalcancerlivermetastasis AT zhengjiang sequentialtreatmentwithactivinandhepatocytegrowthfactorinducesfoxm1topromotecolorectalcancerlivermetastasis AT jinjunguo sequentialtreatmentwithactivinandhepatocytegrowthfactorinducesfoxm1topromotecolorectalcancerlivermetastasis |