Translational Control in Tumour Progression and Drug Resistance

Protein biosynthesis is a multi-step process that starts with the transcription of nuclear DNA, depository of genetic information, into messenger RNA (mRNA) that is used as template for the following polypeptide chain synthesis, also known as translation. Each step of this essential process is highly controlled in order to modulate any specific protein requirement of the cell in response to different stimuli and cellular events. This regulatory process is called translational control. Deregulation of the core signalling network in translational control, the phosphatidyl inositol trisphosphate kinase (PI3K), Protein Kinase B (PKB or Akt), mammalian target of rapamycin (mTOR) and RAS mitogen-activated protein kinase (MAPK)/MAPK-interacting Kinases (MNK) pathways, frequently occurs in human cancers and leads to aberrant modulation of mRNA translation. However, investigations on the contribution of these two pathways to translational regulation led to the interesting finding that translation factors are also substrate of signalling molecules. Post-translational modifications, including cleavage and phosphorylation, usually affect translational factors activity in protein biosynthesis; on the other hand, direct interaction of translational components with signalling mediators can either activate the pathway in which the mediator is involved or redirect translation factors to other activities, such as cytoskeletal rearrangements. These findings shed light on new functions of translation factors, different from their canonical role in protein synthesis. Taken together, these new functions are an intriguing step forward to the discovery of molecular mechanisms at the base of cellular response during “special” conditions such as cancer and drug resistance.