Aberrant vesicular trafficking contributes to altered polarity and metabolism in cancer

Epithelial cancers demonstrate loss of cell polarity, hyperproliferation, and altered cellular metabolism due to acquisition of a suite of genomic aberrations as well as a consequence of metabolic challenges in the tumor microenvironment. Whether these neoplastic properties represent a coordinate process leading to tumor initiation and progression is still poorly understood. In this review, we posit that abnormal vesicular trafficking targets cellular metabolism not just by altering trafficking of receptor tyrosine kinases and nutrient transporters but also by disrupting tight junctions and cell polarity. Apical-basal polarity is required for the formation of normal cellular structures that maintain cellular junctions as well as to regulate asymmetric division of stem cells; disruption of these processes contributes to tumor initiation and progression. Indeed, derailed endocytosis and subsequent aberrations in targeting of vesicles and their cargoes to the correct intracellular compartments is an emerging hallmark of cancer. This chapter will review existing literature to highlight the vicious nexus between trafficking, polarity, and metabolism in order to identify potential Achilles heels that can be exploited therapeutically.