Role Of G1P3-Induced Mitochondrial Reactive Oxygen Species In Cancer Cell Migration
dc.contributor.advisor | Hynds, DiAnna | |
dc.contributor.committeeMember | Averitt, Dayna L; Hanson, Laura; Cheriyath, Venugopalan; Anderson, Mary | |
dc.contributor.committeeMember | Hanson, Laura | |
dc.contributor.committeeMember | Anderson, Mary | |
dc.contributor.committeeMember | Cheriyath, Venugopalan | |
dc.creator | Davenport, Anne M 1968- | |
dc.date.accessioned | 2023-06-28T19:37:40Z | |
dc.date.available | 2023-06-28T19:37:40Z | |
dc.date.created | 2023-05 | |
dc.date.issued | May 2023 | |
dc.date.submitted | May 2023 | |
dc.date.updated | 2023-06-28T19:37:41Z | |
dc.description.abstract | Breast cancer remains the second leading cause of cancer-related deaths among U.S women with metastasis accounting for ˃ 90% of those deaths. G1P3 (IFI6/ISG6-16) is an interferon-stimulated gene encoding a 13 kDa protein with pleiotropic functions. We and others characterized G1P3 as an anti-apoptotic protein located in the mitochondria with a role in cancer progression and metastasis. In accordance with its mitochondrial location, ectopically expressed G1P3 in breast cancer cells (MCF-7G1P3), resulted in elevated levels of mitochondrial reactive species (mtROS) and remodeled actin, potentiating augmented migration. Both scavenging of mtROS and down-regulation of G1P3 expression significantly reduced the migration of MCF-7G1P3 cells. Comparative gene expression analysis identified the upregulation of Caveolin 1 (CAV1), a regulator of wound healing, by 4-fold (p ≤ 0.05) in MCF-7G1P3 cells. Knock-down of CAV1 with small interfering RNA (siRNA) resulted in reduced migration (p ≤ 0.05) and filopodia formation (p ≤ 0.01) in MCF-7G1P3 cells compared to MCF-7Vector cells. Considering filopodia is the predominant migratory structure in MCF-7G1P3 cells and CDC42 is a regulator of filopodia formation and can mediate cell motility, its role in cell migration was assessed. Relative to MCF-7Vector cells, suppression of CDC42 expression significantly reduced migration in MCF-7G1P3 cells (p ≤ 0.05). In G-Lisa assays, MCF-7G1P3 cells had increased GTP-bound CDC42 compared to MCF-7Vector cells which could be reversed with knockdown of Caveolin 1 and G1P3, as well as scavenging of mtROS with MitoTEMPO. In agreement with G1P3’s pleiotropic functions, in confocal microscopy studies, G1P3-FLAG co-occurred with mitochondria as well as organelles of the endomembrane system, including trans-Golgi, lysosomes, endoplasmic reticulum and endosomes. In particular, 52% of G1P3-FLAG co-occurred with RAB5 positive endosomes. RAB5 has been reported to locate to the mitochondria during events of cell stress. In MCF-7G1P3 cells, RAB5 co-occurred with mitochondria ~1.9-fold more than MCF-7Vector cells suggesting that RAB5 may play a role in conferring cell survival in MCF-7G1P3 cells. In conclusion, this study demonstrates that elevated mtROS generated in MCF-7G1P3 cells can alter gene expression to mediate formation of actin structures and augmented migration and metastatic potential in breast cancer cells. | |
dc.format.mimetype | application/pdf | |
dc.identifier.uri | ||
dc.identifier.uri | https://hdl.handle.net/11274/15179 | |
dc.language.iso | English | |
dc.subject | Subjects | |
dc.subject.other | G1P3; mitochondrial reactive oxygen species; breast cancer | |
dc.title | Role Of G1P3-Induced Mitochondrial Reactive Oxygen Species In Cancer Cell Migration | |
dc.type | Thesis | |
dc.type.material | text | |
thesis.degree.college | College of Arts and Sciences | |
thesis.degree.department | School of the Sciences | |
thesis.degree.discipline | Molecular Biology | |
thesis.degree.grantor | Texas Woman's University | |
thesis.degree.name | Doctor of Philosophy | |
thesis.degree.program | AMA 11th edition | |
thesis.degree.school | Texas Woman's University |
Files
Original bundle
1 - 1 of 1
No Thumbnail Available
- Name:
- DAVENPORT-PRIMARY-2023.pdf
- Size:
- 2.38 MB
- Format:
- Adobe Portable Document Format