Role of the E3 ubiquitin ligase RNF125 in pancreatic cancer
Abstracts
Initial Award Abstract |
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Growing evidence points to the role of tobacco smoking pancreatic cancer (PanC). Bring one of the most aggressive tumors that lacks effective therapy and markers for early detection, the proposed studies will focus on understanding a newly identified regulatory pathway in PanC.
The foundation for the proposed research was our discovery that the proteins RNF125 and NR5A2 are expressed at higher levels in PanC than in normal tissue, suggesting they may be involved in cancer development. Indeed, decreasing the levels of these proteins in PanC killed many cells and inhibited tumors in mice. These observations led to the current application to study this novel RNF125/NR5A2 regulatory pathway in PanC, with attention to patients with a smoking history.
Further justification for our study comes from the finding that RNF125 and NR5A2 are expressed at abnormally high or low levels in lung cancer and other smoking-related disorders, including emphysema and steroid-resistant chronic obstructive pulmonary disease. These observations suggest that understanding the RNF125/NR5A2 pathway in PanC will have direct implications for other smoking-related cancers and disorders.
Our proposed studies will analyze mouse and human PanC cells in culture and in mouse models. We will identify proteins that are responsive to RNF125, NR5A2, allowing us to understand how they affect tumor growth, metastasis, and response to chemotherapeutic drugs. We will define their significance for PanC. At all phases of our study, we will work with prominent oncologists, who will provide guidance on the significance and possible implications of our findings.
Completion of our proposed studies is expected to identify novel markers for pancreatic cancer. Our studies will increase our understanding of the mechanisms underlying pancreatic cancer development and metastasis, thereby identifying potential novel therapeutics to improve clinical management of this and other smoking-related disorders. |
