Role of G1P3/IFI6 in Regulating Cytoplasmic DNA and Its Impact on Estrogen Receptor-Positive Breast Cancer Cell Line MCF-7
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Biological and Environmental Sciences
Date of Award
9-1-2026
Abstract
Breast cancer ranks as the second most common cancer among women, and one out of eight women are prone to develop breast cancer in their lifetime. Studies from our group and others identified that G1P3/IFI6, an interferon (IFN), and estrogen-stimulated gene, promotes ER+ breast cancer cells by suppressing apoptosis. However, the mechanisms by which G1P3 regulates cytoplasmic DNA; an important trigger for cell death and immune signaling is unexplored. We hypothesized that G1P3 reduces cytoplasmic DNA levels by enhancing lysosomal-mediated clearance to confer survival advantage. Confocal microscopy showed that MCF-7/G1P3-overexpressing cells have less cytoplasmic DNA compared to MCF-7/Vector. Conversely, siRNA-mediated knockdown of G1P3 increased cytoplasmic DNA in MCF-7/G1P3 cells. To assess whether mtROS mediates G1P3’s effect on cytoplasmic DNA, cells were treated with Mito-TEMPO; however, no significant changes were observed, indicating that G1P3’s effect is independent of mtROS. Co-occurrence of cytoplasmic DNA with LAMP 1 was less in G1P3 overpexpressing cells, however bafilomycin A1, an inhibitor for autophagy, increased co-occurrence of cytoplasmic DNA and LAMP 1 in MCF-7/G1P3 cells, indicating that G1P3 facilitates the trafficking of cytoplasmic DNA to lysosomes for degradation. Additionally, interferon-β treatment reduced cytoplasmic DNA levels, while G1P3 knockdown reversed this effect, highlighting its importance in interferon signaling. Taken together, our study identified the role of G1P3 to promote cytoplasmic DNA clearance by lysosome and inhibiting mtDNA leakage into cytoplasm, emphasizing its potential as a novel therapeutic target aimed at destabilizing lysosomal function and mitochondrial integrity, thereby undermining the survival benefits it confers to cancer cells.
Advisor
Venugopalan Cheriyath
Subject Categories
Biology | Life Sciences
Recommended Citation
Agyabeng, Emmanuel Asirifi, "Role of G1P3/IFI6 in Regulating Cytoplasmic DNA and Its Impact on Estrogen Receptor-Positive Breast Cancer Cell Line MCF-7" (2026). Electronic Theses & Dissertations. 1375.
https://lair.etamu.edu/etd/1375
