Biology
Permanent URI for this collectionhttps://hdl.handle.net/11274/15791
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Browsing Biology by Author "Anderson, Mary"
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Item Role Of G1P3-Induced Mitochondrial Reactive Oxygen Species In Cancer Cell Migration(May 2023) Davenport, Anne M 1968-; Hynds, DiAnna; Averitt, Dayna L; Hanson, Laura; Cheriyath, Venugopalan; Anderson, Mary; Hanson, Laura; Anderson, Mary; Cheriyath, VenugopalanBreast 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.Item Saccharomyces cerevisiae synthesizes ribosomal RNA using RNA polymerase II during nitrogen deprivation(12/30/2016) Vallabhaneni, Arjuna Rao; Conrad-Webb, Heather; Anderson, Mary; Bergel, Michael; Hanson, Laura K.; Mills, NatItem The role of HMGN1 in nucleotide excision repair of human cells: Mechanisms and possible applications(12/30/2015) Lawrence, LaTondra J.; Bergel, Michael; Mills, Nathaniel; Anderson, Mary; Conrad-Webb, Heather; Maier, Camelia