G1P3 Dysregulates Interferon-Stimulated Gene Expression in ER (+) Breast Cancer Cells

Author

• Karina Santana, East Texas A&M UniversityFollow

Document Type

Honors Thesis

Degree Name

Bachelor of Science

Date of Award

4-15-2026

Abstract

Even with advances in diagnosis and treatment, breast cancer remains the second leading cause of cancer-related death in women, with nearly 90% of fatalities linked to drug resistance driven by metastasis and recurrence. G1P3, an anti-apoptotic mitochondrial protein, is upregulated in breast cancer and has been associated with increased metastatic potential and poor prognosis. Recent findings show that G1P3 enhances interactions between Rab5-containing endosomes (RCEs) and mitochondria, and emerging evidence suggests that mitochondria play a critical role in initiating interferon (IFN) responses. Based on this, we hypothesized that G1P3-mediated interactions between RCEs and mitochondria promote interferon-stimulated gene (ISG) expression in breast cancer cells. To test this, we compared ISG expression in the control (MCF-7/Vector) and G1P3-overexpressing (MCF-7/G1P3) breast cancer cells using qRT-PCR following IFN treatment at 0, 2, and 4 hours. Relative to controls, IFIT1, ISG15, and IFI27 were significantly upregulated in MCF-7/G1P3 cells, whereas SCL1, OAS1, ISG20, MX1, and TNFSF10 were downregulated. Furthermore, G1P3- overexpressing cells exhibited a more pronounced, gene-specific ISG expression in response to IFN stimulation. Western blot analysis confirmed that ISG15 was also upregulated at the protein level in MCF-7/G1P3 cells, supporting its transcriptional findings. As a key ubiquitin-like modifier involved in interferon signaling, ISG15 represents a functionally relevant marker of interferon pathway activation and is oncogenic and resistant to chemotherapy at elevated levels. Future studies could expand upon these findings by evaluating additional ISGs at the protein level to define the mechanisms, including the role of RCE-mitochondria interactions and unctional consequences of G1P3-mediated interferon signaling. In summary, our results identify a novel role for G1P3 as a regulator of ISG expression and suggest that its constitutive expression may dysregulate interferon signaling. Targeting G1P3 could therefore, enhance the therapeutic efficacy of interferons while mitigating proinflammatory effects.

Advisor

Venu Cheriyath

Recommended Citation

Santana, Karina, "G1P3 Dysregulates Interferon-Stimulated Gene Expression in ER (+) Breast Cancer Cells" (2026). Honors Theses. 287.
https://lair.etamu.edu/honorstheses/287