Reduced FRG1 expression promotes angiogenesis via activation of the FGF2‐mediated ERK/AKT pathway
Identifying novel targets that control both tumorigenesis and angiogenesis can aid in developing a more potent anti‐angiogenic therapeutic strategy. We previously reported that reduction of FRG1 is associated with increased p38‐MAPK signaling in prostate cancer and with elevated MEK–ERK signaling in...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-05-01
|
| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.13582 |
| _version_ | 1797834973892313088 |
|---|---|
| author | Bratati Mukherjee Pratush Brahma Talina Mohapatra Saurabh Chawla Manjusha Dixit |
| author_facet | Bratati Mukherjee Pratush Brahma Talina Mohapatra Saurabh Chawla Manjusha Dixit |
| author_sort | Bratati Mukherjee |
| collection | DOAJ |
| description | Identifying novel targets that control both tumorigenesis and angiogenesis can aid in developing a more potent anti‐angiogenic therapeutic strategy. We previously reported that reduction of FRG1 is associated with increased p38‐MAPK signaling in prostate cancer and with elevated MEK–ERK signaling in breast cancer. Here, we reveal the role of FRG1 in tumor angiogenesis. Our findings demonstrate that depleted FRG1 levels enhance the proliferation, migration, and tubule formation of HUVECs in a paracrine manner, and this was further substantiated in multiple animal models. Mechanistically, FRG1 depletion activated the expression of FGF2 in breast cancer cells, which triggered the ERK/AKT cascade in endothelial cells. As FRG1 affects multiple tumorigenic properties and it is upstream of FGF2, it can be explored as a therapeutic target that is less prone to resistance. |
| first_indexed | 2024-04-09T14:47:08Z |
| format | Article |
| id | doaj.art-da0f9a2273964097a8d13b6271ad5046 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-04-09T14:47:08Z |
| publishDate | 2023-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-da0f9a2273964097a8d13b6271ad50462023-05-02T14:40:52ZengWileyFEBS Open Bio2211-54632023-05-0113580481710.1002/2211-5463.13582Reduced FRG1 expression promotes angiogenesis via activation of the FGF2‐mediated ERK/AKT pathwayBratati Mukherjee0Pratush Brahma1Talina Mohapatra2Saurabh Chawla3Manjusha Dixit4Cancer and Angiogenesis Research Lab, School of Biological Sciences National Institute of Science Education and Research Bhubaneswar IndiaCancer and Angiogenesis Research Lab, School of Biological Sciences National Institute of Science Education and Research Bhubaneswar IndiaCancer and Angiogenesis Research Lab, School of Biological Sciences National Institute of Science Education and Research Bhubaneswar IndiaCancer and Angiogenesis Research Lab, School of Biological Sciences National Institute of Science Education and Research Bhubaneswar IndiaCancer and Angiogenesis Research Lab, School of Biological Sciences National Institute of Science Education and Research Bhubaneswar IndiaIdentifying novel targets that control both tumorigenesis and angiogenesis can aid in developing a more potent anti‐angiogenic therapeutic strategy. We previously reported that reduction of FRG1 is associated with increased p38‐MAPK signaling in prostate cancer and with elevated MEK–ERK signaling in breast cancer. Here, we reveal the role of FRG1 in tumor angiogenesis. Our findings demonstrate that depleted FRG1 levels enhance the proliferation, migration, and tubule formation of HUVECs in a paracrine manner, and this was further substantiated in multiple animal models. Mechanistically, FRG1 depletion activated the expression of FGF2 in breast cancer cells, which triggered the ERK/AKT cascade in endothelial cells. As FRG1 affects multiple tumorigenic properties and it is upstream of FGF2, it can be explored as a therapeutic target that is less prone to resistance.https://doi.org/10.1002/2211-5463.13582angiogenesisbreast cancerERK/AKT signalingFGF2FRG1HUVECs |
| spellingShingle | Bratati Mukherjee Pratush Brahma Talina Mohapatra Saurabh Chawla Manjusha Dixit Reduced FRG1 expression promotes angiogenesis via activation of the FGF2‐mediated ERK/AKT pathway FEBS Open Bio angiogenesis breast cancer ERK/AKT signaling FGF2 FRG1 HUVECs |
| title | Reduced FRG1 expression promotes angiogenesis via activation of the FGF2‐mediated ERK/AKT pathway |
| title_full | Reduced FRG1 expression promotes angiogenesis via activation of the FGF2‐mediated ERK/AKT pathway |
| title_fullStr | Reduced FRG1 expression promotes angiogenesis via activation of the FGF2‐mediated ERK/AKT pathway |
| title_full_unstemmed | Reduced FRG1 expression promotes angiogenesis via activation of the FGF2‐mediated ERK/AKT pathway |
| title_short | Reduced FRG1 expression promotes angiogenesis via activation of the FGF2‐mediated ERK/AKT pathway |
| title_sort | reduced frg1 expression promotes angiogenesis via activation of the fgf2 mediated erk akt pathway |
| topic | angiogenesis breast cancer ERK/AKT signaling FGF2 FRG1 HUVECs |
| url | https://doi.org/10.1002/2211-5463.13582 |
| work_keys_str_mv | AT bratatimukherjee reducedfrg1expressionpromotesangiogenesisviaactivationofthefgf2mediatederkaktpathway AT pratushbrahma reducedfrg1expressionpromotesangiogenesisviaactivationofthefgf2mediatederkaktpathway AT talinamohapatra reducedfrg1expressionpromotesangiogenesisviaactivationofthefgf2mediatederkaktpathway AT saurabhchawla reducedfrg1expressionpromotesangiogenesisviaactivationofthefgf2mediatederkaktpathway AT manjushadixit reducedfrg1expressionpromotesangiogenesisviaactivationofthefgf2mediatederkaktpathway |