Metabolic Fluxes in Cancer Metabolism

Since Otto Warburg’s work almost a century ago, we have known that cancer cells undergo a metabolic transformation that makes them convert the majority of their glucose carbon into lactate. In the past decade it has become clear that this metabolic signat

  • PDF / 788,973 Bytes
  • 34 Pages / 439.37 x 666.142 pts Page_size
  • 75 Downloads / 210 Views

DOWNLOAD

REPORT


Metabolic Fluxes in Cancer Metabolism Ulrich L. Gu¨nther, Mei G. Chong, Tatiana Volpari, Katarzyna M. Koczula, Karen Atkins, Christopher M. Bunce, and Farhat L. Khanim

Contents 14.1 14.2

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Metabolic Pathways and Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.2.1 Aspects of Altered Metabolism in Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.2.2 Adaptation of Cancer Metabolism to a Hypoxic Tumor Environment . . . . . . . 14.2.3 Oncogenes and Tumor Suppressors Coupled to Metabolic Reprogramming 14.2.4 Cancer Mutations Promoting the Warburg Effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.3 Metabolic Flux Analysis in Studying Cancer Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.3.1 Historical Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.3.2 Technologies Used for MFA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.3.3 Recent Approaches for MFA Using NMR Methods . . . . . . . . . . . . . . . . . . . . . . . . . . 14.4 Applications of MFA in Cancer Cell Lines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.5 Metabolic Fluxes In Vivo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.6 Summary and Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

316 318 318 320 321 323 325 325 326 330 332 337 339 340

U.L. Gu¨nther (*) • M.G. Chong • T. Volpari • K.M. Koczula • K. Atkins School of Cancer Sciences, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, United Kingdom e-mail: [email protected] C.M. Bunce • F.L. Khanim School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom © Springer-Verlag Wien 2015 S. Mazurek, M. Shoshan (eds.), Tumor Cell Metabolism, DOI 10.1007/978-3-7091-1824-5_14

315

U.L. Gu¨nther et al.

316

14.1

Introduction

Malignant cells undergo a metabolic transformation to satisfy the demands of growth and proliferation. This was first recognized by Otto Warburg who discovered that rapidly proliferating ascite tumors produce large amounts of lactate through fermentation, even in the presence of oxygen (Warburg et al. 1926a; Warburg 1956a; Koppenol et al. 2011). He postulated injury of respiration as the cause of cancer. This phenomenon, termed the Warburg effect, has been observed for many t