Defining the Glyco-RNAome in Melanoma Progression
Abstract
Cells attach sugar molecules to proteins to regulate their function and localization. The machinery that controls the attachment of sugars is often perturbed in cancers such as melanoma, rendering tumor cells more aggressive and metastatic and invisible to the immune system. A recent study reported that sugar molecules can also be attached to RNAs and that such glyco-RNAs decorate the outside of cells, likely to be presented to the cells’ surroundings. However, the molecular functions of glyco-RNAs and their effect on the interaction of cancer cells with their host are completely unknown. In this Idea Award application, we propose to identify glyco-RNAs that play important roles in the aggressive behavior of melanoma cells. Importantly, sugar modification of RNAs may be controlled by dietary intake of sugars, such as fucose, to reduce the risk of melanoma formation and metastasis. Thus, characterizing the roles of glyco-RNAs in melanoma aligns well with the fiscal year 2022 (FY22) Melanoma Research Program (MRP) Challenge Statement. Moreover, since glyco-RNAs are presented at the cell surface where they interact with the environment and immune cells, which could affect progression and metastasis, our study directly addresses two FY22 MRP Focus Areas: Identify how the tumor microenvironment impacts tumor initiation, response to therapy, progression, recurrence, and/or dormancy and Delineate the molecular pathways that influence metastatic spread, recurrence, and/or dormancy. Our studies will uncover a completely unrecognized new dimension of RNA and glycobiology, and there is tremendous potential for discoveries that will have a significant impact on these aspects of melanoma biology and thus offer new avenues for therapeutic intervention. For instance, by controlling the dietary consumption of certain sugars, the risk of melanoma patients to develop recurrent or metastatic disease could be lowered. This Idea Award will enable us to define and lead the burgeoning glyco-RNA field and to improve our understanding of how the interaction of melanoma cells with their environment provokes more aggressive disease. This knowledge, in turn, will be instrumental in developing new ideas to limit these interactions for melanoma prevention and therapeutic intervention. This will significantly benefit active-duty Service Members and Veterans who, due to their service at locations with high UV indexes, are at a higher risk of developing melanoma.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310513
Entities
People
- Florian Karreth
Organizations
- H. Lee Moffitt Cancer Center & Research Institute
- United States Army