Molecular connections between metabolism, epigenetics, and cell cycle: Cancer Cell Methionine Dependency
This research project seeks molecular understanding of how a key metabolic pathway communicates with the cell cycle machinery. We have chosen the metabolic pathway around methionine and the principal methyl-group donor S-adensoylmethionine (SAM). Sufficient SAM concentrations are critical for duplication of epigenetic methylation marks, and the cell cycle has developed mechanisms to receive input about SAM availability. This research extends the concept of cell cycle checkpoints by defining a metabolite-controlled checkpoint important for epigenetic stability (SAM-checkpoint). Interestingly, our studies have demonstrated that SAMcheckpoint activation is the underlying cause for “methionine-dependency of cancer”, and we tightly connected this metabolic phenomenon to the tumorigenic phenotype. Addiction of cancer to certain metabolic pathways promises to present novel targets for cancer therapeutics. The dependence of cancer on high levels of SAM may be a therapeutically interesting weakness of tumors.
What happened to the cancer cells? Aberrant Splicing during methionine stress: Workflow
Aberrant Splicing during methionine stress: Visualization
MB468 and R8 cells has distinct gene expression profile
Gene expression heatmap of splicing related genes
