Cancer metabolism meets systems biology: Understanding metabolic master regulators

3^rd International Conference and Exhibition on Metabolomics & Systems Biology

March 24-26, 2014 Hilton San Antonio Airport, San Antonio, USA

Fabian V. Filipp

Scientific Tracks Abstracts: Metabolomics

Abstract :

Pyruvate kinase activity is controlled by a tightly woven regulatory network. The oncofetal isoform of pyruvate kinase (PKM2) is a master regulator of cancer metabolism. PKM2 engages in parallel, feed‑forward, positive and negative feedback control contributing to cancer progression. Besides its metabolic role, non‑metabolic functions of PKM2 as protein kinase and transcriptional coactivator for c‑MYC and hypoxia‑inducible factor 1‑alpha are essential for epidermal growth factor receptor activation‑induced tumorigenesis. These biochemical activities are controlled by a shift in the oligomeric state of PKM2 that includes acetylation, oxidation, phosphorylation, prolyl hydroxylation and sumoylation. Metabolically active PKM2 tetramer is allosterically regulated and responds to nutritional and stress signals. Metabolically inactive PKM2 dimer is imported into the nucleus and can function as protein kinase stimulating transcription. A systems biology approach to PKM2 at the genome, transcriptome, proteome, metabolome and fluxome level reveals how differences in biomolecular structure translate into a global rewiring of cancer metabolism. Cancer systems biology takes us beyond the Warburg effect, opening unprecedented therapeutic opportunities.

Biography :

Page 52 Volume 4, Issue 2 Metabolomics 2014 ISSN: 2153-0769, JOM an open access journal Metabolomics-2014 March 24-26, 2014 March 24-26, 2014 Hilton San Antonio Airport, San Antonio, USA 3 rd International Conference and Exhibition on Metabolomics & Systems Biology Fabian V. Filipp, Metabolomics 2014, 4:2 http://dx.doi.org/10.4172/2153-0769.S1.024 Cancer metabolism meets systems biology: Understanding metabolic master regulators Fabian V. Filipp University of California Merced, USA P yruvate kinase activity is controlled by a tightly woven regulatory network. The oncofetal isoform of pyruvate kinase (PKM2) is a master regulator of cancer metabolism. PKM2 engages in parallel, feed‑forward, positive and negative feedback control contributing to cancer progression. Besides its metabolic role, non‑metabolic functions of PKM2 as protein kinase and transcriptional coactivator for c‑MYC and hypoxia‑inducible factor 1‑alpha are essential for epidermal growth factor receptor activation‑induced tumorigenesis. These biochemical activities are controlled by a shift in the oligomeric state of PKM2 that includes acetylation, oxidation, phosphorylation, prolyl hydroxylation and sumoylation. Metabolically active PKM2 tetramer is allosterically regulated and responds to nutritional and stress signals. Metabolically inactive PKM2 dimer is imported into the nucleus and can function as protein kinase stimulating transcription. A systems biology approach to PKM2 at the genome, transcriptome, proteome, metabolome and fluxome level reveals how differences in biomolecular structure translate into a global rewiring of cancer metabolism. Cancer systems biology takes us beyond the Warburg effect, opening unprecedented therapeutic opportunities. Biography