Maintenance of Endoplasmic Reticulum Protein Homeostasis in Cancer: Friend or Foe

The endoplasmic reticulum, as the site of synthesis for proteins in the secretory pathway has evolved select machineries to ensure the correct folding and modification of proteins. However, sometimes these quality control mechanisms fail and proteins are misfolded. Other factors, such as nutrient deprivation, hypoxia or an increased demand on protein synthesis can also cause the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum. There are mechanisms that recognise and deal with this accumulation of protein through degradation and/or export. Many diseases are associated with aberrant quality control mechanisms, and among these, cancer has emerged as a group of diseases that rely on endoplasmic reticulum homeostasis to sustain development and growth. The knowledge of how protein quality control operates in cancer has identified opportunities for these pathways to be pharmacologically targeted, which could lead to newer or more effective treatments in the future.