Ets1 facilitates EMT/invasion through Drp1-mediated mitochondrial fragmentation in ovarian cancer
Summary: Ovarian cancer has sustained as a major cause of cancer-related female mortality owing to its aggressive nature and a dearth of early detection markers. Ets1 oncoprotein, a transcription factor belonging to the Ets family, is a well-established promoter of epithelial to mesenchymal transiti...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223016140 |
| _version_ | 1797740889484820480 |
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| author | Deepshikha Ghosh Suman Pakhira Damayanti Das Ghosh Susanta Roychoudhury Sib Sankar Roy |
| author_facet | Deepshikha Ghosh Suman Pakhira Damayanti Das Ghosh Susanta Roychoudhury Sib Sankar Roy |
| author_sort | Deepshikha Ghosh |
| collection | DOAJ |
| description | Summary: Ovarian cancer has sustained as a major cause of cancer-related female mortality owing to its aggressive nature and a dearth of early detection markers. Ets1 oncoprotein, a transcription factor belonging to the Ets family, is a well-established promoter of epithelial to mesenchymal transition (EMT) and a prospective malignancy marker in ovarian cancer. Our study establishes Ets1 as a regulator of mitochondrial fission-fusion dynamics through Drp1 augmentation via direct binding at DNM1L (DRP1) promoter. Ets1 overexpression-mediated Drp1 increment resulted in mitochondrial load reduction and compromised OXPHOS Complex 5 (ATP synthase) expression, facilitating a greater reliance on glycolysis over OXPHOS. Furthermore, our work demonstrates that inhibition of mitochondrial fission through molecular or pharmacological inhibition of Drp1 successfully mitigates Ets1-associated EMT in both in vitro and in vivo syngeneic mice model. Collectively, our data highlight the role of Drp1-mediated mitochondrial fragmentation in driving Ets1-mediated bioenergetic alterations and EMT/invasion in ovarian cancer. |
| first_indexed | 2024-03-12T14:19:01Z |
| format | Article |
| id | doaj.art-ed7ff5fc813843e49fea4fc294c40965 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T14:19:01Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-ed7ff5fc813843e49fea4fc294c409652023-08-20T04:38:26ZengElsevieriScience2589-00422023-09-01269107537Ets1 facilitates EMT/invasion through Drp1-mediated mitochondrial fragmentation in ovarian cancerDeepshikha Ghosh0Suman Pakhira1Damayanti Das Ghosh2Susanta Roychoudhury3Sib Sankar Roy4Cell Biology and Physiology Division, CSIR Indian Institute of Chemical Biology (CSIR IICB), 4, Raja S.C. Mullick Road, Kolkata 700032, IndiaCell Biology and Physiology Division, CSIR Indian Institute of Chemical Biology (CSIR IICB), 4, Raja S.C. Mullick Road, Kolkata 700032, IndiaMolecular and Diagnostics Laboratory, Basic and Translational Research, Saroj Gupta Cancer Centre & Research Institute, Thakurpukur, Kolkata 700063, IndiaCell Biology and Physiology Division, CSIR Indian Institute of Chemical Biology (CSIR IICB), 4, Raja S.C. Mullick Road, Kolkata 700032, IndiaCell Biology and Physiology Division, CSIR Indian Institute of Chemical Biology (CSIR IICB), 4, Raja S.C. Mullick Road, Kolkata 700032, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India; Corresponding authorSummary: Ovarian cancer has sustained as a major cause of cancer-related female mortality owing to its aggressive nature and a dearth of early detection markers. Ets1 oncoprotein, a transcription factor belonging to the Ets family, is a well-established promoter of epithelial to mesenchymal transition (EMT) and a prospective malignancy marker in ovarian cancer. Our study establishes Ets1 as a regulator of mitochondrial fission-fusion dynamics through Drp1 augmentation via direct binding at DNM1L (DRP1) promoter. Ets1 overexpression-mediated Drp1 increment resulted in mitochondrial load reduction and compromised OXPHOS Complex 5 (ATP synthase) expression, facilitating a greater reliance on glycolysis over OXPHOS. Furthermore, our work demonstrates that inhibition of mitochondrial fission through molecular or pharmacological inhibition of Drp1 successfully mitigates Ets1-associated EMT in both in vitro and in vivo syngeneic mice model. Collectively, our data highlight the role of Drp1-mediated mitochondrial fragmentation in driving Ets1-mediated bioenergetic alterations and EMT/invasion in ovarian cancer.http://www.sciencedirect.com/science/article/pii/S2589004223016140Molecular biologyCancer |
| spellingShingle | Deepshikha Ghosh Suman Pakhira Damayanti Das Ghosh Susanta Roychoudhury Sib Sankar Roy Ets1 facilitates EMT/invasion through Drp1-mediated mitochondrial fragmentation in ovarian cancer iScience Molecular biology Cancer |
| title | Ets1 facilitates EMT/invasion through Drp1-mediated mitochondrial fragmentation in ovarian cancer |
| title_full | Ets1 facilitates EMT/invasion through Drp1-mediated mitochondrial fragmentation in ovarian cancer |
| title_fullStr | Ets1 facilitates EMT/invasion through Drp1-mediated mitochondrial fragmentation in ovarian cancer |
| title_full_unstemmed | Ets1 facilitates EMT/invasion through Drp1-mediated mitochondrial fragmentation in ovarian cancer |
| title_short | Ets1 facilitates EMT/invasion through Drp1-mediated mitochondrial fragmentation in ovarian cancer |
| title_sort | ets1 facilitates emt invasion through drp1 mediated mitochondrial fragmentation in ovarian cancer |
| topic | Molecular biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223016140 |
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