G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer
Epigenetic abnormalities affect tumor progression, as well as gene expression and function. Among the diverse epigenetic modulators, the histone methyltransferase G9a has been focused on due to its role in accelerating tumorigenesis and metastasis. Although epigenetic dysregulation is closely relate...
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2022-01-01
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author | Yunho Jin Shinji Park Soon-Yong Park Chae-Young Lee Da-Young Eum Jae-Woong Shim Si-Ho Choi Yoo-Jin Choi Seong-Joon Park Kyu Heo |
author_facet | Yunho Jin Shinji Park Soon-Yong Park Chae-Young Lee Da-Young Eum Jae-Woong Shim Si-Ho Choi Yoo-Jin Choi Seong-Joon Park Kyu Heo |
author_sort | Yunho Jin |
collection | DOAJ |
description | Epigenetic abnormalities affect tumor progression, as well as gene expression and function. Among the diverse epigenetic modulators, the histone methyltransferase G9a has been focused on due to its role in accelerating tumorigenesis and metastasis. Although epigenetic dysregulation is closely related to tumor progression, reports regarding the relationship between G9a and its possible downstream factors regulating breast tumor growth are scarce. Therefore, we aimed to verify the role of G9a and its presumable downstream regulators during malignant progression of breast cancer. G9a-depleted MCF7 and T47D breast cancer cells exhibited suppressed motility, including migration and invasion, and an improved response to ionizing radiation. To identify the possible key factors underlying these effects, microarray analysis was performed, and a TGF-β superfamily member, BMP5, was selected as a prominent target gene. It was found that BMP5 expression was markedly increased by G9a knockdown. Moreover, reduction in the migration/invasion ability of MCF7 and T47D breast cancer cells was induced by BMP5. Interestingly, a G9a-depletion-mediated increase in BMP5 expression induced the phosphorylation of Smad proteins, which are the intracellular signaling mediators of BMP5. Accordingly, we concluded that the observed antitumor effects may be based on the G9a-depletion-mediated increase in BMP5 expression and the consequent facilitation of Smad protein phosphorylation. |
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spelling | doaj.art-8d10906420494f359373855252c12b1b2023-11-23T14:00:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-0123258910.3390/ijms23020589G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast CancerYunho Jin0Shinji Park1Soon-Yong Park2Chae-Young Lee3Da-Young Eum4Jae-Woong Shim5Si-Ho Choi6Yoo-Jin Choi7Seong-Joon Park8Kyu Heo9Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaEpigenetic abnormalities affect tumor progression, as well as gene expression and function. Among the diverse epigenetic modulators, the histone methyltransferase G9a has been focused on due to its role in accelerating tumorigenesis and metastasis. Although epigenetic dysregulation is closely related to tumor progression, reports regarding the relationship between G9a and its possible downstream factors regulating breast tumor growth are scarce. Therefore, we aimed to verify the role of G9a and its presumable downstream regulators during malignant progression of breast cancer. G9a-depleted MCF7 and T47D breast cancer cells exhibited suppressed motility, including migration and invasion, and an improved response to ionizing radiation. To identify the possible key factors underlying these effects, microarray analysis was performed, and a TGF-β superfamily member, BMP5, was selected as a prominent target gene. It was found that BMP5 expression was markedly increased by G9a knockdown. Moreover, reduction in the migration/invasion ability of MCF7 and T47D breast cancer cells was induced by BMP5. Interestingly, a G9a-depletion-mediated increase in BMP5 expression induced the phosphorylation of Smad proteins, which are the intracellular signaling mediators of BMP5. Accordingly, we concluded that the observed antitumor effects may be based on the G9a-depletion-mediated increase in BMP5 expression and the consequent facilitation of Smad protein phosphorylation.https://www.mdpi.com/1422-0067/23/2/589breast cancerepigeneticsG9aBMP5 |
spellingShingle | Yunho Jin Shinji Park Soon-Yong Park Chae-Young Lee Da-Young Eum Jae-Woong Shim Si-Ho Choi Yoo-Jin Choi Seong-Joon Park Kyu Heo G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer International Journal of Molecular Sciences breast cancer epigenetics G9a BMP5 |
title | G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer |
title_full | G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer |
title_fullStr | G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer |
title_full_unstemmed | G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer |
title_short | G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer |
title_sort | g9a knockdown suppresses cancer aggressiveness by facilitating smad protein phosphorylation through increasing bmp5 expression in luminal a type breast cancer |
topic | breast cancer epigenetics G9a BMP5 |
url | https://www.mdpi.com/1422-0067/23/2/589 |
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