Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways
Abstract Background Metastasis is a major cause of death in human colorectal cancer patients. However, the contribution of chemokines in the tumor microenvironment to tumor metastasis is not fully understood. Methods Herein, we examinined several chemokines in colorectal cancer patients using chemok...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-03-01
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| Series: | Molecular Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12943-017-0629-4 |
| _version_ | 1817986016756105216 |
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| author | Jingkun Zhao Baochi Ou Dingpei Han Puxiongzhi Wang Yaping Zong Congcong Zhu Di Liu Minhua Zheng Jing Sun Hao Feng Aiguo Lu |
| author_facet | Jingkun Zhao Baochi Ou Dingpei Han Puxiongzhi Wang Yaping Zong Congcong Zhu Di Liu Minhua Zheng Jing Sun Hao Feng Aiguo Lu |
| author_sort | Jingkun Zhao |
| collection | DOAJ |
| description | Abstract Background Metastasis is a major cause of death in human colorectal cancer patients. However, the contribution of chemokines in the tumor microenvironment to tumor metastasis is not fully understood. Methods Herein, we examinined several chemokines in colorectal cancer patients using chemokine ELISA array. Immunohistochemistry was used to detect expression of CXCL5 in colorectal cancer patients tissues. Human HCT116 and SW480 cell lines stably transfected with CXCL5, shCXCL5 and shCXCR2 lentivirus plasmids were used in our in vitro study. Immunoblot, immunofluorescence and transwell assay were used to examine the molecular biology and morphological changes in these cells. In addition, we used nude mice to detect the influence of CXCL5 on tumor metastasis in vivo. Results We found that CXCL5 was overexpressed in tumor tissues and associated with advanced tumor stage as well as poor prognosis in colorectal cancer patients. We also demonstrated that CXCL5 was primarily expressed in the tumor cell cytoplasm and cell membranes, which may indicate that the CXCL5 was predominantly produced by cancer epithelial cells instead of fibroblasts in the tumor mesenchyme. Additionally, overexpression of CXCL5 enhanced the migration and invasion of colorectal cancer cells by inducing the epithelial-mesenchymal transition (EMT) through activation of the ERK/Elk-1/Snail pathway and the AKT/GSK3β/β-catenin pathway in a CXCR2-dependent manner. The silencing of Snail and β-catenin attenuated CXCL5/CXCR2-enhanced cell migration and invasion in vitro. The elevated expression of CXCL5 can also potentiate the metastasis of colorectal cancer cells to the liver in vivo in nude mice intrasplenic injection model. Conclusion In conclusion, our findings support CXCL5 as a promoter of colorectal cancer metastasis and a predictor of poor clinical outcomes in colorectal cancer patients. |
| first_indexed | 2024-04-14T00:05:03Z |
| format | Article |
| id | doaj.art-908779e22e61471a9ae86ee26a0bd626 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-04-14T00:05:03Z |
| publishDate | 2017-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-908779e22e61471a9ae86ee26a0bd6262022-12-22T02:23:34ZengBMCMolecular Cancer1476-45982017-03-0116111510.1186/s12943-017-0629-4Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathwaysJingkun Zhao0Baochi Ou1Dingpei Han2Puxiongzhi Wang3Yaping Zong4Congcong Zhu5Di Liu6Minhua Zheng7Jing Sun8Hao Feng9Aiguo Lu10Shanghai Minimally Invasive Surgery Center, Ruijin hospital, Shanghai Jiaotong University School of MedicineShanghai Minimally Invasive Surgery Center, Ruijin hospital, Shanghai Jiaotong University School of MedicineDepartment of thoracic surgery, Ruijin hospital, Shanghai Jiaotong University School of MedicineShanghai Minimally Invasive Surgery Center, Ruijin hospital, Shanghai Jiaotong University School of MedicineShanghai Minimally Invasive Surgery Center, Ruijin hospital, Shanghai Jiaotong University School of MedicineShanghai Minimally Invasive Surgery Center, Ruijin hospital, Shanghai Jiaotong University School of MedicineShanghai Minimally Invasive Surgery Center, Ruijin hospital, Shanghai Jiaotong University School of MedicineShanghai Minimally Invasive Surgery Center, Ruijin hospital, Shanghai Jiaotong University School of MedicineShanghai Minimally Invasive Surgery Center, Ruijin hospital, Shanghai Jiaotong University School of MedicineDepartment of General, Visceral, Transplantation, and Vascular Thoracic Surgery, Hospital of University of LMU MunichShanghai Minimally Invasive Surgery Center, Ruijin hospital, Shanghai Jiaotong University School of MedicineAbstract Background Metastasis is a major cause of death in human colorectal cancer patients. However, the contribution of chemokines in the tumor microenvironment to tumor metastasis is not fully understood. Methods Herein, we examinined several chemokines in colorectal cancer patients using chemokine ELISA array. Immunohistochemistry was used to detect expression of CXCL5 in colorectal cancer patients tissues. Human HCT116 and SW480 cell lines stably transfected with CXCL5, shCXCL5 and shCXCR2 lentivirus plasmids were used in our in vitro study. Immunoblot, immunofluorescence and transwell assay were used to examine the molecular biology and morphological changes in these cells. In addition, we used nude mice to detect the influence of CXCL5 on tumor metastasis in vivo. Results We found that CXCL5 was overexpressed in tumor tissues and associated with advanced tumor stage as well as poor prognosis in colorectal cancer patients. We also demonstrated that CXCL5 was primarily expressed in the tumor cell cytoplasm and cell membranes, which may indicate that the CXCL5 was predominantly produced by cancer epithelial cells instead of fibroblasts in the tumor mesenchyme. Additionally, overexpression of CXCL5 enhanced the migration and invasion of colorectal cancer cells by inducing the epithelial-mesenchymal transition (EMT) through activation of the ERK/Elk-1/Snail pathway and the AKT/GSK3β/β-catenin pathway in a CXCR2-dependent manner. The silencing of Snail and β-catenin attenuated CXCL5/CXCR2-enhanced cell migration and invasion in vitro. The elevated expression of CXCL5 can also potentiate the metastasis of colorectal cancer cells to the liver in vivo in nude mice intrasplenic injection model. Conclusion In conclusion, our findings support CXCL5 as a promoter of colorectal cancer metastasis and a predictor of poor clinical outcomes in colorectal cancer patients.http://link.springer.com/article/10.1186/s12943-017-0629-4CXCL5Colorectal cancerEMTSnailβ-catenin |
| spellingShingle | Jingkun Zhao Baochi Ou Dingpei Han Puxiongzhi Wang Yaping Zong Congcong Zhu Di Liu Minhua Zheng Jing Sun Hao Feng Aiguo Lu Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways Molecular Cancer CXCL5 Colorectal cancer EMT Snail β-catenin |
| title | Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways |
| title_full | Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways |
| title_fullStr | Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways |
| title_full_unstemmed | Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways |
| title_short | Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways |
| title_sort | tumor derived cxcl5 promotes human colorectal cancer metastasis through activation of the erk elk 1 snail and akt gsk3β β catenin pathways |
| topic | CXCL5 Colorectal cancer EMT Snail β-catenin |
| url | http://link.springer.com/article/10.1186/s12943-017-0629-4 |
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