Abstract

Notwithstanding that metabolic perturbations and dysregulated protein synthesis are salient features of cancer, the mechanism underlying coordination of cellular energy balance with mRNA translation (which is the most energy consuming process in the cell) is poorly understood. In this review, we focus on recently emerging insights in the molecular underpinnings of the cross-talk between oncogenic kinases, translational apparatus and cellular energy metabolism. In particular, we focus on the central signaling nodes that regulate these processes (e.g. the mechanistic/mammalian target of rapamycin MTOR) and the potential implications of these findings on improving the anti-neoplastic efficacy of oncogenic kinase inhibitors.

Highlights

  • Protein synthesis is a complex process involving the interaction of ribosomes, mRNAs, tRNAs and auxiliary proteins known as translation factors (Hershey et al 2012)

  • The function and/or the expression of several components of the translation machinery is perturbed in cancer cells (Ruggero 2013)

  • The role of MTOR in the regulation of mitochondrial biogenesis and activity Considering that mRNA translation is a highly energyconsuming cellular process, it is closely coordinated with cellular energy production (Topisirovic & Sonenberg 2011)

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Summary

Introduction

Protein synthesis is a complex process involving the interaction of ribosomes, mRNAs, tRNAs and auxiliary proteins known as translation factors (Hershey et al 2012). Protein synthesis must be tightly regulated as it affects crucial cellular processes (e.g. proliferation, growth, differentiation and development) (Hershey et al 2012). Dysregulated mRNA translation is implicated in most hallmarks of cancer including aberrant cell proliferation, survival, angiogenesis and cellular energetics (Johnson et al 1976, Kevil et al 1996, Larsson et al 2006, Larsson et al 2007, Hanahan & Weinberg 2011, Topisirovic & Sonenberg 2011). A positive correlation has been observed between cancer cell proliferation and the rate of protein synthesis (Johnson et al 1976). The function and/or the expression of several components of the translation machinery is perturbed in cancer cells (Ruggero 2013).

Printed in Great Britain
Cancer metabolism and therapeutic implications
Future perspectives
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