Overexpression of FERM Domain Containing Kindlin 2 (FERMT2) in Fibroblasts Correlates with EMT and Immunosuppression in Gastric Cancer
The mesenchymal feature, dominated by epithelial mesenchymal transition (EMT) and stromal cell activation, is one of the main reasons for the aggressive nature of tumors, yet it remains poorly understood. In gastric cancer (GC), the fermitin family homolog-2 (FERMT2) is involved in macrophage signal...
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | International Journal of Genomics |
| Online Access: | http://dx.doi.org/10.1155/2024/4123737 |
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| _version_ | 1832559556677337088 |
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| author | Sheng-yan Yin Yuan-jie Liu Jie-pin Li Jian Liu |
| author_facet | Sheng-yan Yin Yuan-jie Liu Jie-pin Li Jian Liu |
| author_sort | Sheng-yan Yin |
| collection | DOAJ |
| description | The mesenchymal feature, dominated by epithelial mesenchymal transition (EMT) and stromal cell activation, is one of the main reasons for the aggressive nature of tumors, yet it remains poorly understood. In gastric cancer (GC), the fermitin family homolog-2 (FERMT2) is involved in macrophage signaling, promoting migration and invasion. However, the function of FERMT2 in fibroblasts remains unclear. Here, we demonstrated that downregulation of FERMT2 expression can block EMT in GC cells by inhibiting fibroblast activation in vitro. Furthermore, we found that, in addition to the known pathways, fibroblast-derived FERMT2 promotes M2-like macrophage growth and that in human GC samples, there is a strong positive correlation between FERMT2 and CD163 and CD206 levels. Notably, high FERMT2 expression was significantly associated with poor clinical outcomes and was upregulated in patients with advanced disease. Taken together, our results provide evidence that the fibroblast-FERMT2-EMT-M2 macrophage axis plays a critical role in the GC mesenchymal phenotype and may be a promising target for the treatment of advanced GC. |
| format | Article |
| id | doaj-art-5e00da6c886e4af68e8763ee735d8685 |
| institution | Kabale University |
| issn | 2314-4378 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Genomics |
| spelling | doaj-art-5e00da6c886e4af68e8763ee735d86852025-02-03T01:29:48ZengWileyInternational Journal of Genomics2314-43782024-01-01202410.1155/2024/4123737Overexpression of FERM Domain Containing Kindlin 2 (FERMT2) in Fibroblasts Correlates with EMT and Immunosuppression in Gastric CancerSheng-yan Yin0Yuan-jie Liu1Jie-pin Li2Jian Liu3The Second Affiliated Hospital of Nanjing University of Chinese MedicineThe Second Affiliated Hospital of Nanjing University of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese MedicineThe Second Affiliated Hospital of Nanjing University of Chinese MedicineThe mesenchymal feature, dominated by epithelial mesenchymal transition (EMT) and stromal cell activation, is one of the main reasons for the aggressive nature of tumors, yet it remains poorly understood. In gastric cancer (GC), the fermitin family homolog-2 (FERMT2) is involved in macrophage signaling, promoting migration and invasion. However, the function of FERMT2 in fibroblasts remains unclear. Here, we demonstrated that downregulation of FERMT2 expression can block EMT in GC cells by inhibiting fibroblast activation in vitro. Furthermore, we found that, in addition to the known pathways, fibroblast-derived FERMT2 promotes M2-like macrophage growth and that in human GC samples, there is a strong positive correlation between FERMT2 and CD163 and CD206 levels. Notably, high FERMT2 expression was significantly associated with poor clinical outcomes and was upregulated in patients with advanced disease. Taken together, our results provide evidence that the fibroblast-FERMT2-EMT-M2 macrophage axis plays a critical role in the GC mesenchymal phenotype and may be a promising target for the treatment of advanced GC.http://dx.doi.org/10.1155/2024/4123737 |
| spellingShingle | Sheng-yan Yin Yuan-jie Liu Jie-pin Li Jian Liu Overexpression of FERM Domain Containing Kindlin 2 (FERMT2) in Fibroblasts Correlates with EMT and Immunosuppression in Gastric Cancer International Journal of Genomics |
| title | Overexpression of FERM Domain Containing Kindlin 2 (FERMT2) in Fibroblasts Correlates with EMT and Immunosuppression in Gastric Cancer |
| title_full | Overexpression of FERM Domain Containing Kindlin 2 (FERMT2) in Fibroblasts Correlates with EMT and Immunosuppression in Gastric Cancer |
| title_fullStr | Overexpression of FERM Domain Containing Kindlin 2 (FERMT2) in Fibroblasts Correlates with EMT and Immunosuppression in Gastric Cancer |
| title_full_unstemmed | Overexpression of FERM Domain Containing Kindlin 2 (FERMT2) in Fibroblasts Correlates with EMT and Immunosuppression in Gastric Cancer |
| title_short | Overexpression of FERM Domain Containing Kindlin 2 (FERMT2) in Fibroblasts Correlates with EMT and Immunosuppression in Gastric Cancer |
| title_sort | overexpression of ferm domain containing kindlin 2 fermt2 in fibroblasts correlates with emt and immunosuppression in gastric cancer |
| url | http://dx.doi.org/10.1155/2024/4123737 |
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