Translation initiation and its relationship with metabolic mechanisms in cancer development, progression and...

Pathways that regulate protein homeostasis (proteostasis) in cells range from mRNA processing to protein degradation; perturbations in regulatory mechanisms of these pathways can lead to oncogenic cellular processes. Protein synthesis modulation failures are common phenomena in cancer cells, wherein specific conditions that promote the translation of protein factors promoting carcinogenesis are present. These specific conditions may be favored by metabolic lipid alterations like those found in metabolic syndrome and obesity. Protein translation modifications have been described in obesity, favoring the translation of protein targets that benefit lipid accumulation; a determining factor is the activity of the cap-binding eukaryotic translation initiation factor 4E (eIF4E), a crosstalk in protein translation and lipogenesis. Besides, alterations of protein translation initiation steps are critical participants for the development of both pathogenic conditions, cancer, and obesity. This chapter is focused on the regulation of recognition and processing of carcinogenic-mRNA and the connections among lipid metabolism and cell signaling pathways that promote oncogenesis, tumoral microenvironment generation and potentially the development of chemoresistance. We performed an in-depth analysis of events, such as those occurring in obesity and dyslipidemias, that may influence protein translation, driving the recognition of certain mRNAs and favoring cancer development and chemoresistance.