PLOD3 facilitated T cell activation in the colorectal tumor microenvironment and liver metastasis by the TNF-α/ NF-κB pathway
Abstract Background Colorectal cancer (CRC) has been the third most prevalent cancer worldwide. Liver metastasis is the critical factor for the poor prognosis of CRC. Here, we investigated the expression and role of PLOD3 in CRC. Methods Different liver metastasis models were established by injectin...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-01-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04809-w |
| _version_ | 1797362935652155392 |
|---|---|
| author | Min Ding Cheng Wang Junhong Hu Junjun She Ruoyu Shi Yixuan Liu Qi Sun Haojun Xu Guoren Zhou Wenlan Wu Hongping Xia |
| author_facet | Min Ding Cheng Wang Junhong Hu Junjun She Ruoyu Shi Yixuan Liu Qi Sun Haojun Xu Guoren Zhou Wenlan Wu Hongping Xia |
| author_sort | Min Ding |
| collection | DOAJ |
| description | Abstract Background Colorectal cancer (CRC) has been the third most prevalent cancer worldwide. Liver metastasis is the critical factor for the poor prognosis of CRC. Here, we investigated the expression and role of PLOD3 in CRC. Methods Different liver metastasis models were established by injecting PLOD3 stable knockdown or overexpression CT26 or MC38 mouse CRC cells into the spleen of mice to verify the tumorigenicity and metastasis ability in vivo. Results We identified PLOD3 is significantly overexpressed in liver metastasis samples of CRC. High expression of PLOD3 was significantly associated with poor survival of CRC patients. The knockdown of PLOD3 exhibited remarkable inhibition of proliferation, migration, and invasion in CRC cells, while the opposite results could be found in different PLOD3-overexpressed CRC cells. Stable knockdown of PLOD3 also significantly inhibited liver metastasis of CRC cells in different xenografts models, while stable overexpression of PLOD3 promotes liver metastasis and tumor progression. Further studies showed that PLOD3 facilitated the T cell activation in the tumor microenvironment and affected the TNF-α/ NF-κB pathway. Conclusions This study revealed the essential biological functions of PLOD3 in colon cancer progression and metastasis, suggesting that PLOD3 is a promising translational medicine target and bioengineering targeting PLOD3 overcomes CRC liver metastasis. Graphical Abstract |
| first_indexed | 2024-03-08T16:14:34Z |
| format | Article |
| id | doaj.art-a19fb40964204c80b500be0304a56832 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-08T16:14:34Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-a19fb40964204c80b500be0304a568322024-01-07T12:42:07ZengBMCJournal of Translational Medicine1479-58762024-01-0122111610.1186/s12967-023-04809-wPLOD3 facilitated T cell activation in the colorectal tumor microenvironment and liver metastasis by the TNF-α/ NF-κB pathwayMin Ding0Cheng Wang1Junhong Hu2Junjun She3Ruoyu Shi4Yixuan Liu5Qi Sun6Haojun Xu7Guoren Zhou8Wenlan Wu9Hongping Xia10Department of Pathology & Nanjing Drum Tower Hospital Clinical College & Key Laboratory of Antibody Technique of National Health Commission && Jiangsu Antibody Drug Engineering Research Center, Nanjing Medical UniversityDepartment of Pathology & Nanjing Drum Tower Hospital Clinical College & Key Laboratory of Antibody Technique of National Health Commission && Jiangsu Antibody Drug Engineering Research Center, Nanjing Medical UniversityDepartment of Colorectal and Anal Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of General Surgery & High Talent & Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Anatomical Pathology, Singapore General HospitalDepartment of Pathology & Nanjing Drum Tower Hospital Clinical College & Key Laboratory of Antibody Technique of National Health Commission && Jiangsu Antibody Drug Engineering Research Center, Nanjing Medical UniversityDepartment of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolDepartment of Pathology & Nanjing Drum Tower Hospital Clinical College & Key Laboratory of Antibody Technique of National Health Commission && Jiangsu Antibody Drug Engineering Research Center, Nanjing Medical UniversityJiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer ResearchJiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer ResearchDepartment of Pathology & Nanjing Drum Tower Hospital Clinical College & Key Laboratory of Antibody Technique of National Health Commission && Jiangsu Antibody Drug Engineering Research Center, Nanjing Medical UniversityAbstract Background Colorectal cancer (CRC) has been the third most prevalent cancer worldwide. Liver metastasis is the critical factor for the poor prognosis of CRC. Here, we investigated the expression and role of PLOD3 in CRC. Methods Different liver metastasis models were established by injecting PLOD3 stable knockdown or overexpression CT26 or MC38 mouse CRC cells into the spleen of mice to verify the tumorigenicity and metastasis ability in vivo. Results We identified PLOD3 is significantly overexpressed in liver metastasis samples of CRC. High expression of PLOD3 was significantly associated with poor survival of CRC patients. The knockdown of PLOD3 exhibited remarkable inhibition of proliferation, migration, and invasion in CRC cells, while the opposite results could be found in different PLOD3-overexpressed CRC cells. Stable knockdown of PLOD3 also significantly inhibited liver metastasis of CRC cells in different xenografts models, while stable overexpression of PLOD3 promotes liver metastasis and tumor progression. Further studies showed that PLOD3 facilitated the T cell activation in the tumor microenvironment and affected the TNF-α/ NF-κB pathway. Conclusions This study revealed the essential biological functions of PLOD3 in colon cancer progression and metastasis, suggesting that PLOD3 is a promising translational medicine target and bioengineering targeting PLOD3 overcomes CRC liver metastasis. Graphical Abstracthttps://doi.org/10.1186/s12967-023-04809-wPLOD3Colorectal cancerLiver metastasisProliferationNF-κB |
| spellingShingle | Min Ding Cheng Wang Junhong Hu Junjun She Ruoyu Shi Yixuan Liu Qi Sun Haojun Xu Guoren Zhou Wenlan Wu Hongping Xia PLOD3 facilitated T cell activation in the colorectal tumor microenvironment and liver metastasis by the TNF-α/ NF-κB pathway Journal of Translational Medicine PLOD3 Colorectal cancer Liver metastasis Proliferation NF-κB |
| title | PLOD3 facilitated T cell activation in the colorectal tumor microenvironment and liver metastasis by the TNF-α/ NF-κB pathway |
| title_full | PLOD3 facilitated T cell activation in the colorectal tumor microenvironment and liver metastasis by the TNF-α/ NF-κB pathway |
| title_fullStr | PLOD3 facilitated T cell activation in the colorectal tumor microenvironment and liver metastasis by the TNF-α/ NF-κB pathway |
| title_full_unstemmed | PLOD3 facilitated T cell activation in the colorectal tumor microenvironment and liver metastasis by the TNF-α/ NF-κB pathway |
| title_short | PLOD3 facilitated T cell activation in the colorectal tumor microenvironment and liver metastasis by the TNF-α/ NF-κB pathway |
| title_sort | plod3 facilitated t cell activation in the colorectal tumor microenvironment and liver metastasis by the tnf α nf κb pathway |
| topic | PLOD3 Colorectal cancer Liver metastasis Proliferation NF-κB |
| url | https://doi.org/10.1186/s12967-023-04809-w |
| work_keys_str_mv | AT minding plod3facilitatedtcellactivationinthecolorectaltumormicroenvironmentandlivermetastasisbythetnfanfkbpathway AT chengwang plod3facilitatedtcellactivationinthecolorectaltumormicroenvironmentandlivermetastasisbythetnfanfkbpathway AT junhonghu plod3facilitatedtcellactivationinthecolorectaltumormicroenvironmentandlivermetastasisbythetnfanfkbpathway AT junjunshe plod3facilitatedtcellactivationinthecolorectaltumormicroenvironmentandlivermetastasisbythetnfanfkbpathway AT ruoyushi plod3facilitatedtcellactivationinthecolorectaltumormicroenvironmentandlivermetastasisbythetnfanfkbpathway AT yixuanliu plod3facilitatedtcellactivationinthecolorectaltumormicroenvironmentandlivermetastasisbythetnfanfkbpathway AT qisun plod3facilitatedtcellactivationinthecolorectaltumormicroenvironmentandlivermetastasisbythetnfanfkbpathway AT haojunxu plod3facilitatedtcellactivationinthecolorectaltumormicroenvironmentandlivermetastasisbythetnfanfkbpathway AT guorenzhou plod3facilitatedtcellactivationinthecolorectaltumormicroenvironmentandlivermetastasisbythetnfanfkbpathway AT wenlanwu plod3facilitatedtcellactivationinthecolorectaltumormicroenvironmentandlivermetastasisbythetnfanfkbpathway AT hongpingxia plod3facilitatedtcellactivationinthecolorectaltumormicroenvironmentandlivermetastasisbythetnfanfkbpathway |