On metabolic reprogramming and tumor biology: A comprehensive survey of metabolism in breast cancer
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Judith Penkert1, Tim Ripperger1, Maximilian Schieck1, Brigitte Schlegelberger1, Doris Steinemann1 and Thomas Illig1,2
1 Institute of Human Genetics, Hannover Medical School, Hannover, Germany
2 Hannover Unified Biobank, Hannover Medical School, Hannover, Germany
Thomas Illig, email:
Keywords: cancer metabolism, breast cancer, metabolomics, cancer microenvironment, tumor heterogeneity
Received: May 31, 2016 Accepted: August 25, 2016 Published: August 31, 2016
Altered metabolism in tumor cells has been a focus of cancer research for as long as a century but has remained controversial and vague due to an inhomogeneous overall picture. Accumulating genomic, metabolomic, and lastly panomic data as well as bioenergetics studies of the past few years enable a more comprehensive, systems-biologic approach promoting deeper insight into tumor biology and challenging hitherto existing models of cancer bioenergetics. Presenting a compendium on breast cancer-specific metabolome analyses performed thus far, we review and compile currently known aspects of breast cancer biology into a comprehensive network, elucidating previously dissonant issues of cancer metabolism. As such, some of the aspects critically discussed in this review include the dynamic interplay or metabolic coupling between cancer (stem) cells and cancer-associated fibroblasts, the intratumoral and intertumoral heterogeneity and plasticity of cancer cell metabolism, the existence of distinct metabolic tumor compartments in need of separate yet simultaneous therapeutic targeting, the reliance of cancer cells on oxidative metabolism and mitochondrial power, and the role of pro-inflammatory, pro-tumorigenic stromal conditioning. Comprising complex breast cancer signaling networks as well as combined metabolomic and genomic data, we address metabolic consequences of mutations in tumor suppressor genes and evaluate their contribution to breast cancer predisposition in a germline setting, reasoning for distinct personalized preventive and therapeutic measures. The review closes with a discussion on central root mechanisms of tumor cell metabolism and rate-limiting steps thereof, introducing essential strategies for therapeutic targeting.
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