Method for screening of compounds to modulate glycolysis in cancer cells
Prof. Matthias Hentze, European Molecular Biology Laboratory (EMBL); Dr Ina Huppertz, European Molecular Biology Laboratory (EMBL)
EMBLEM Technology Transfer GmbH
Despite tremendous efforts and progress on cancer studies and treatments of the past decades, the disease remains a major cause of death in humans. Current therapeutic options include surgery, radiation therapy, chemotherapy and immunotherapy. All of these treatment options are associated with major side effects and bear the risk of the cancer developing resistance. This implies the persisting need to develop novel treatment approaches.
Most cancer cells rely on glycolysis for energy supply which led to an increased interest in this classical pathway and its regulation for treatments in oncology. Enolase 1 (ENO1) is a glycolytic enzyme ubiquitously expressed in adult human tissues that catalyses the reversible interconversion between 2-phosphoglycerate (2-PG) and phosphoenolpyruvate (PEP). The overexpression of ENO1 has been associated with multiple tumours and has therefore become an interesting target for the development of new compounds.
Researchers at EMBL Heidelberg studied the regulation of ENO1 in connection with RNA and could show that ENO1 binds RNA in human cells. The study further revealed specific cellular RNA ligands that inhibit ENO1’s activity in vitro and in cells. The results therefore establish ENO1’s riboregulation as a novel form of metabolic control.
As another aspect of the study, the results demonstrated physiological importance of ENO1’s riboregulation during mouse embryonic stem cell (mESC) differentiation, and therefore reveals a novel form of regulated cell differentiation. The tools developed in the course of the project led to a platform for screening and characterization of compounds for the treatment of cancer or other proliferative diseases by modulation ENO1’s activity, and for the identification of substances to control stem cell differentiation.
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The technology has been demonstrated in HeLa cells and mESCs.
A priority patent application has been filed.