Reciprocal Dynamics of Metabolism and mRNA Translation in Tumor Angiogenesis

Abstract

Angiogenesis, the process of formation of new blood vessels from pre-existing vasculature, is essential for tumor growth and metastasis. Anti-angiogenic treatment targeting vascular endothelial growth factor (VEGF) signaling is a powerful tool to combat tumor growth; however, anti-tumor angiogenesis therapy has shown limited efficacy, with survival benefits ranging from only a few weeks to months. Compensation by upregulation of complementary growth factors and switches to different modes of vascularization have made these types of therapies less effective. Recent evidence suggests that targeting specific players in endothelial metabolism is a valuable therapeutic strategy against tumor angiogenesis. Although it is clear that metabolism can modulate the translational machinery, the reciprocal relationship between metabolism and mRNA translational control during tumor angiogenesis is not fully understood. In this review, we explore emerging examples of how endothelial cell metabolism affects mRNA translation during the formation of blood vessels. A deeper comprehension of these mechanisms could lead to the development of innovative therapeutic strategies for both physiological and pathological angiogenesis.

Keywords: endothelial cell metabolism; mRNA translation; tumor vasculature.

Figure 1

Crosstalk between endothelial cell metabolism and mRNA translation during tumor angiogenesis. The angiogenic activity of endothelial cells depends on their metabolic state, which influences the translational apparatus. Four translational actors—Cap-dependent regulation of translation, integrated stress response (ISR), stress granule (SG) formation and tRNA metabolism—are exquisitely controlled by metabolism and play a crucial role in endothelial cells (ECs), influencing vasculature formation. Some elements of the figure were created with BioRender.com.