The objective of this proposal is to characterize the cancer-specific alteration of a metabolic complex of human glucose metabolism and its functional contribution to cancer cell metabolism. Recent advances in our knowledge of the spatial assemblies of metabolic enzymes in cells have suggested that metabolism may benefit from spatial compartmentalization. Recently, we demonstrated the formation of a metabolic complex by the enzymes involved in human glucose metabolism in cells; namely the glucosome. Importantly, we have noticed the formation of large-sized glucosome clusters in the cytoplasm of various human cancer cells, but not in non-cancerous, normal human cell lines. We hypothesize that the large-sized clusters of glucosomes are cancer-specific and thus functionally essential for cancer cell metabolism. To test this hypothesis, in Aim1, we will determine the cancer specificity of the large-sized clusters by analyzing the degree of the large-sized cluster formation and its impacts on metabolic profiles from various human cancer and non-cancerous cell lines.
In Aim 2, we will detail size-dependent functional contribution of the glucosome clusters to cancer cell metabolism. We will carry out quantitative single-cell analyses with various fluorescence microscopic techniques and also 13C-metabolic flux analysis with mass spectrometry. The proposed research using both single-cell and ensemble measurements will uncover unprecedented mechanistic insights of the spatial alteration of glucose metabolism at single cancer cell levels. This new level of understanding will divulge the importance of a heretofore unrecognized metabolic complex, the glucosome, as a novel target for anti-cancer therapeutic intervention. Collectively, successful application of the proposed research will accelerate our efforts in translating our basic cancer research into novel drug discovery for the treatment of human cancer.

Public Health Relevance

Dysregulated glucose metabolism is a hallmark of human cancer. We propose to characterize cancer-specific alteration of a metabolic complex of human glucose metabolism in cancer cells and its functional significance to cancer cell metabolism. This new level of understanding will divulge the importance of a heretofore unrecognized metabolic complex as a novel target for therapeutic intervention.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
1R03CA219609-01A1
Application #
9590379
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Spalholz, Barbara A
Project Start
2018-07-03
Project End
2020-06-30
Budget Start
2018-07-03
Budget End
2019-06-30
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Maryland Balt CO Campus
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
061364808
City
Baltimore
State
MD
Country
United States
Zip Code
21250