Reduced FRG1 expression promotes prostate cancer progression and affects prostate cancer cell migration and invasion
Abstract Background Prostate cancer is the most common form of cancer in males and accounts for high cancer related deaths. Therapeutic advancement in prostate cancer has not been able to reduce the mortality burden of prostate cancer, which warrants further research. FRG1 which affects angiogenesis...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-04-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-019-5509-4 |
| _version_ | 1811198571485069312 |
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| author | Ankit Tiwari Bratati Mukherjee Md. Khurshidul Hassan Niharika Pattanaik Archita Mohanty Jaiswal Manjusha Dixit |
| author_facet | Ankit Tiwari Bratati Mukherjee Md. Khurshidul Hassan Niharika Pattanaik Archita Mohanty Jaiswal Manjusha Dixit |
| author_sort | Ankit Tiwari |
| collection | DOAJ |
| description | Abstract Background Prostate cancer is the most common form of cancer in males and accounts for high cancer related deaths. Therapeutic advancement in prostate cancer has not been able to reduce the mortality burden of prostate cancer, which warrants further research. FRG1 which affects angiogenesis and cell migration in Xenopus, can be a potential player in tumorigenesis. In this study, we investigated the role of FRG1 in prostate cancer progression. Methods Immunohistochemistry was performed to determine FRG1 expression in patient samples. FRG1 expression perturbation was done to investigate the effect of FRG1 on cell proliferation, migration and invasion, in DU145, PC3 and LNCaP cells. To understand the mechanism, we checked expression of various cytokines and MMPs by q-RT PCR, signaling molecules by western blot, in FRG1 perturbation sets. Results were validated by use of pharmacological inhibitor and activator and, western blot. Results In prostate cancer tissue, FRG1 levels were significantly reduced, compared to the uninvolved counterpart. FRG1 expression showed variable effect on PC3 and DU145 cell proliferation. FRG1 levels consistently affected cell migration and invasion, in both DU145 and PC3 cells. Ectopic expression of FRG1 led to significant reduction in cell migration and invasion in both DU145 and PC3 cells, reverse trends were observed with FRG1 knockdown. In androgen receptor positive cell line LNCaP, FRG1 doesn’t affect any of the cell properties. FRG1 knockdown led to significantly enhanced expression of GM-CSF, MMP1, PDGFA and CXCL1, in PC3 cells and, in DU145, it led to higher expression of GM-CSF, MMP1 and PLGF. Interestingly, FRG1 knockdown in both the cell lines led to activation of p38 MAPK. Pharmacological activation of p38 MAPK led to increase in the expression of GM-CSF and PLGF in DU145 whereas in PC3 it led to enhanced expression of GM-CSF, MMP1 and CXCL1. On the other hand, inhibition of p38 MAPK led to reduction in the expression of above mentioned cytokines. Conclusion FRG1 expression is reduced in prostate adenocarcinoma tissue. FRG1 expression affects migration and invasion in AR negative prostate cancer cells through known MMPs and cytokines, which may be mediated primarily via p38 MAPK activation. |
| first_indexed | 2024-04-12T01:33:47Z |
| format | Article |
| id | doaj.art-302abd85fc4446449225d399de40da11 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T01:33:47Z |
| publishDate | 2019-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-302abd85fc4446449225d399de40da112022-12-22T03:53:23ZengBMCBMC Cancer1471-24072019-04-0119111510.1186/s12885-019-5509-4Reduced FRG1 expression promotes prostate cancer progression and affects prostate cancer cell migration and invasionAnkit Tiwari0Bratati Mukherjee1Md. Khurshidul Hassan2Niharika Pattanaik3Archita Mohanty Jaiswal4Manjusha Dixit5School of Biological Sciences, National Institute of Science Education and Research BhubaneswarSchool of Biological Sciences, National Institute of Science Education and Research BhubaneswarSchool of Biological Sciences, National Institute of Science Education and Research BhubaneswarSRL Diagnostics LtdSRL Diagnostics LtdSchool of Biological Sciences, National Institute of Science Education and Research BhubaneswarAbstract Background Prostate cancer is the most common form of cancer in males and accounts for high cancer related deaths. Therapeutic advancement in prostate cancer has not been able to reduce the mortality burden of prostate cancer, which warrants further research. FRG1 which affects angiogenesis and cell migration in Xenopus, can be a potential player in tumorigenesis. In this study, we investigated the role of FRG1 in prostate cancer progression. Methods Immunohistochemistry was performed to determine FRG1 expression in patient samples. FRG1 expression perturbation was done to investigate the effect of FRG1 on cell proliferation, migration and invasion, in DU145, PC3 and LNCaP cells. To understand the mechanism, we checked expression of various cytokines and MMPs by q-RT PCR, signaling molecules by western blot, in FRG1 perturbation sets. Results were validated by use of pharmacological inhibitor and activator and, western blot. Results In prostate cancer tissue, FRG1 levels were significantly reduced, compared to the uninvolved counterpart. FRG1 expression showed variable effect on PC3 and DU145 cell proliferation. FRG1 levels consistently affected cell migration and invasion, in both DU145 and PC3 cells. Ectopic expression of FRG1 led to significant reduction in cell migration and invasion in both DU145 and PC3 cells, reverse trends were observed with FRG1 knockdown. In androgen receptor positive cell line LNCaP, FRG1 doesn’t affect any of the cell properties. FRG1 knockdown led to significantly enhanced expression of GM-CSF, MMP1, PDGFA and CXCL1, in PC3 cells and, in DU145, it led to higher expression of GM-CSF, MMP1 and PLGF. Interestingly, FRG1 knockdown in both the cell lines led to activation of p38 MAPK. Pharmacological activation of p38 MAPK led to increase in the expression of GM-CSF and PLGF in DU145 whereas in PC3 it led to enhanced expression of GM-CSF, MMP1 and CXCL1. On the other hand, inhibition of p38 MAPK led to reduction in the expression of above mentioned cytokines. Conclusion FRG1 expression is reduced in prostate adenocarcinoma tissue. FRG1 expression affects migration and invasion in AR negative prostate cancer cells through known MMPs and cytokines, which may be mediated primarily via p38 MAPK activation.http://link.springer.com/article/10.1186/s12885-019-5509-4FRG1Prostate cancerImmunohistochemistryCell migrationCell invasionp38 MAPK |
| spellingShingle | Ankit Tiwari Bratati Mukherjee Md. Khurshidul Hassan Niharika Pattanaik Archita Mohanty Jaiswal Manjusha Dixit Reduced FRG1 expression promotes prostate cancer progression and affects prostate cancer cell migration and invasion BMC Cancer FRG1 Prostate cancer Immunohistochemistry Cell migration Cell invasion p38 MAPK |
| title | Reduced FRG1 expression promotes prostate cancer progression and affects prostate cancer cell migration and invasion |
| title_full | Reduced FRG1 expression promotes prostate cancer progression and affects prostate cancer cell migration and invasion |
| title_fullStr | Reduced FRG1 expression promotes prostate cancer progression and affects prostate cancer cell migration and invasion |
| title_full_unstemmed | Reduced FRG1 expression promotes prostate cancer progression and affects prostate cancer cell migration and invasion |
| title_short | Reduced FRG1 expression promotes prostate cancer progression and affects prostate cancer cell migration and invasion |
| title_sort | reduced frg1 expression promotes prostate cancer progression and affects prostate cancer cell migration and invasion |
| topic | FRG1 Prostate cancer Immunohistochemistry Cell migration Cell invasion p38 MAPK |
| url | http://link.springer.com/article/10.1186/s12885-019-5509-4 |
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