| Affiliations: | Genetics & Genomics Research Leadership |
| Project Leader: | Hannah Carter hcarter12@tamu.edu Veterinary Physiology & Pharmacology |
| Faculty Mentor: | Weston Porter, Ph.D |
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Meeting Times:
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TBD |
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Team Size:
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3 |
| Open Spots: | 0 |
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Description:
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Project Description Mitochondria play a crucial role in upholding cellular homeostasis by orchestrating signaling and functional processes in response to both intracellular and extracellular stimuli. Characterizing the mechanisms underlying the regulation of mitochondrial dynamics is critical to understanding the shift in these dynamics across normal development and breast cancer progression in the mammary gland. Our previous studies have highlighted the significance of Singleminded-2s (Sim2s), a member of the bHLH/PAS family, in regulating mitochondrial dynamics during mammary gland development and the progression of estrogen receptor-positive (ER+) breast cancer (BC). Overexpression of Sim2s in mouse mammary epithelial cells leads to alterations in mitochondrial morphology and dynamics resulting in enhanced mitochondrial fusion and elongation. We have identified Sim2s as a tumor suppressor expressed in mammary epithelial cells, known to inhibit epithelial-mesenchymal transition (EMT) and metastasis. Furthermore, we have extended our investigations to MCF7 cells, a human ER+ BC cell line. In our previous studies, we discovered that loss of SIM2s expression in the MCF7 cell line promotes mitochondrial fragmentation [1-9]. In conjunction with these findings, literature suggests that sirtuins also play a role in the regulation of mitochondrial dynamics similar to Sim2s [10]. Specifically, there is an upregulation of Sirtuin 1 (SirT1) in cancer when Sim2 is lost, while Sirtuin 3 (SirT3) increases during differentiation and normal development progression (Fig 3). Sirtuins are a class of enzymes known for their critical involvement in various cellular processes, including those related to mitochondrial function. Specifically, they act as regulators of mitochondrial biogenesis, dynamics, and overall quality control. These enzymes contribute to the maintenance of mitochondrial health by ensuring that damaged or dysfunctional mitochondria are repaired or removed through processes like mitophagy [10]. While there is intriguing evidence suggesting a link between Sim2s, sirtuins, and mitochondrial dynamics in mammary gland development and breast cancer, further research is needed to bridge these gaps and provide a more comprehensive understanding of the underlying mechanisms and potential clinical implications. Therefore, our aim is to elucidate the potential interaction between Singleminded-2s and sirtuins in the regulation of mitochondrial dynamics. We hypothesize that Sim2s modulates mitochondrial function through its association with sirtuins, thereby influencing normal mammary gland development and breast cancer progression. |