A review of the association between osteosarcoma metastasis and protein translation

Abstract

The malignant transformation of mesenchymal cells within the bone leads to the development of osteosarcoma (OS), but the genetic underpinnings of these events are not understood. From a clinical perspective, primary tumour management can be achieved successfully in most patients. However, the development of metastasis to the lungs represents the most common cause of death in OS patients. A clearer understanding of metastasis biology is required to improve cancer mortality and improve outcomes. Modelling the genetics, biology and therapy of OS can be accomplished through research involving a number of species. Most notable is the naturally occurring form of OS that develops in dogs. Through a cross-species and comparative approach important questions can be asked within specific and suitable models to advance our understanding of this disease and its common metastatic outcome. A comparative perspective on the problem of OS metastasis that utilizes a cross-species approach may offer unique opportunities to assist in this prioritization and generate new hypotheses related to this important clinical problem.

Fig. 1

Translational machinery. Under physiological conditions, eIF4E is bound to its inhibitory binding protein 4EBP1. Upon phosphorylation (P) of 4EBP1, eIF4E is liberated from 4EBP1 and able to bind with capped mRNA (7mG) and eIF4G-eIF3-eIF4A subunits, forming the eIF4F complex. eIF4E is the rate-limiting component of the eIF4F complex. eIF4F is a necessary component of the 48S initiation complex. PABP, poly(A) binding protein.