AATF inhibition exerts antiangiogenic effects against human hepatocellular carcinoma
Background and aimsAngiogenesis is a key factor in the growth and metastasis of hepatic tumors and thus a potential therapeutic target in hepatocellular carcinoma (HCC). In this study, we aim to identify the key role of apoptosis antagonizing transcription factor (AATF) in tumor angiogenesis and its...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1130380/full |
| _version_ | 1797808356890509312 |
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| author | Diwakar Suresh Akshatha N. Srinivas Akila Prashant Suchitha Satish Prashant Vishwanath Suma M. Nataraj Srinivas V. Koduru Prasanna K. Santhekadur Divya P. Kumar |
| author_facet | Diwakar Suresh Akshatha N. Srinivas Akila Prashant Suchitha Satish Prashant Vishwanath Suma M. Nataraj Srinivas V. Koduru Prasanna K. Santhekadur Divya P. Kumar |
| author_sort | Diwakar Suresh |
| collection | DOAJ |
| description | Background and aimsAngiogenesis is a key factor in the growth and metastasis of hepatic tumors and thus a potential therapeutic target in hepatocellular carcinoma (HCC). In this study, we aim to identify the key role of apoptosis antagonizing transcription factor (AATF) in tumor angiogenesis and its underlying mechanisms in HCC.MethodsHCC tissues were analyzed for AATF expression by qRT-PCR and immunohistochemistry. Stable clones of control and AATF knockdown (KD) were established in human HCC cells. The effect of AATF inhibition on the angiogenic processes was determined by proliferation, invasion, migration, chick chorioallantoic membrane (CAM) assay, zymography, and immunoblotting techniques.ResultsWe identified high levels of AATF in human HCC tissues compared to adjacent normal liver tissues, and the expression was found to be correlated with the stages and tumor grades of HCC. Inhibiting AATF in QGY-7703 cells resulted in higher levels of pigment epithelium-derived factor (PEDF) than controls due to decreased matric metalloproteinase activity. Conditioned media from AATF KD cells inhibited the proliferation, migration, and invasion of human umbilical vein endothelial cells as well as the vascularization of the chick chorioallantoic membrane. Furthermore, the VEGF-mediated downstream signaling pathway responsible for endothelial cell survival and vascular permeability, cell proliferation, and migration favoring angiogenesis was suppressed by AATF inhibition. Notably, PEDF inhibition effectively reversed the anti-angiogenic effect of AATF KD.ConclusionOur study reports the first evidence that the therapeutic strategy based on the inhibition of AATF to disrupt tumor angiogenesis may serve as a promising approach for HCC treatment. |
| first_indexed | 2024-03-13T06:36:20Z |
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| id | doaj.art-b93adebc1d0b4b4398f5b713bbc62ab1 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-13T06:36:20Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-b93adebc1d0b4b4398f5b713bbc62ab12023-06-09T05:05:34ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-06-011310.3389/fonc.2023.11303801130380AATF inhibition exerts antiangiogenic effects against human hepatocellular carcinomaDiwakar Suresh0Akshatha N. Srinivas1Akila Prashant2Suchitha Satish3Prashant Vishwanath4Suma M. Nataraj5Srinivas V. Koduru6Prasanna K. Santhekadur7Divya P. Kumar8Department of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, IndiaDepartment of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, IndiaDepartment of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, IndiaDepartment of Pathology, JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysuru, IndiaDepartment of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, IndiaDepartment of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, IndiaGene Arrays, Omelette Inc., New York, NY, United StatesDepartment of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, IndiaDepartment of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, IndiaBackground and aimsAngiogenesis is a key factor in the growth and metastasis of hepatic tumors and thus a potential therapeutic target in hepatocellular carcinoma (HCC). In this study, we aim to identify the key role of apoptosis antagonizing transcription factor (AATF) in tumor angiogenesis and its underlying mechanisms in HCC.MethodsHCC tissues were analyzed for AATF expression by qRT-PCR and immunohistochemistry. Stable clones of control and AATF knockdown (KD) were established in human HCC cells. The effect of AATF inhibition on the angiogenic processes was determined by proliferation, invasion, migration, chick chorioallantoic membrane (CAM) assay, zymography, and immunoblotting techniques.ResultsWe identified high levels of AATF in human HCC tissues compared to adjacent normal liver tissues, and the expression was found to be correlated with the stages and tumor grades of HCC. Inhibiting AATF in QGY-7703 cells resulted in higher levels of pigment epithelium-derived factor (PEDF) than controls due to decreased matric metalloproteinase activity. Conditioned media from AATF KD cells inhibited the proliferation, migration, and invasion of human umbilical vein endothelial cells as well as the vascularization of the chick chorioallantoic membrane. Furthermore, the VEGF-mediated downstream signaling pathway responsible for endothelial cell survival and vascular permeability, cell proliferation, and migration favoring angiogenesis was suppressed by AATF inhibition. Notably, PEDF inhibition effectively reversed the anti-angiogenic effect of AATF KD.ConclusionOur study reports the first evidence that the therapeutic strategy based on the inhibition of AATF to disrupt tumor angiogenesis may serve as a promising approach for HCC treatment.https://www.frontiersin.org/articles/10.3389/fonc.2023.1130380/fullapoptosis antagonizing transcription factorangiogenesishepatocellular carcinomaknockdown (KD)human umbilic vein endothelial cells (HUVEC)pigment epithelium derived factor |
| spellingShingle | Diwakar Suresh Akshatha N. Srinivas Akila Prashant Suchitha Satish Prashant Vishwanath Suma M. Nataraj Srinivas V. Koduru Prasanna K. Santhekadur Divya P. Kumar AATF inhibition exerts antiangiogenic effects against human hepatocellular carcinoma Frontiers in Oncology apoptosis antagonizing transcription factor angiogenesis hepatocellular carcinoma knockdown (KD) human umbilic vein endothelial cells (HUVEC) pigment epithelium derived factor |
| title | AATF inhibition exerts antiangiogenic effects against human hepatocellular carcinoma |
| title_full | AATF inhibition exerts antiangiogenic effects against human hepatocellular carcinoma |
| title_fullStr | AATF inhibition exerts antiangiogenic effects against human hepatocellular carcinoma |
| title_full_unstemmed | AATF inhibition exerts antiangiogenic effects against human hepatocellular carcinoma |
| title_short | AATF inhibition exerts antiangiogenic effects against human hepatocellular carcinoma |
| title_sort | aatf inhibition exerts antiangiogenic effects against human hepatocellular carcinoma |
| topic | apoptosis antagonizing transcription factor angiogenesis hepatocellular carcinoma knockdown (KD) human umbilic vein endothelial cells (HUVEC) pigment epithelium derived factor |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1130380/full |
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