The Tubulin Code and Tubulin-Modifying Enzymes in Autophagy and Cancer

Simple Summary Microtubules are tubulin polymers that constitute the structure of eukaryotic cells. They control different cell functions that are often deregulated in cancer, such as cell shape, cell motility and the intracellular movement of organelles. Here, we focus on the crucial role of tubulin modifications in determining different cancer characteristics, including metastatic cell migration and therapy resistance. We also discuss the influence of microtubule modifications on the autophagic process-the cellular degradation pathway that influences cancer growth. We discuss findings showing that inducing microtubule modifications can be used as a means to kill cancer cells by inhibiting autophagy. Microtubules are key components of the cytoskeleton of eukaryotic cells. Microtubule dynamic instability together with the "tubulin code" generated by the choice of different alpha- and beta- tubulin isoforms and tubulin post-translational modifications have essential roles in the control of a variety of cellular processes, such as cell shape, cell motility, and intracellular trafficking, that are deregulated in cancer. In this review, we will discuss available evidence that highlights the crucial role of the tubulin code in determining different cancer phenotypes, including metastatic cell migration, drug resistance, and tumor vascularization, and the influence of modulating tubulin-modifying enzymes on cancer cell survival and aggressiveness. We will also discuss the role of post-translationally modified microtubules in autophagy-the lysosomal-mediated cellular degradation pathway-that exerts a dual role in many cancer types, either promoting or suppressing cancer growth. We will give particular emphasis to the role of tubulin post-translational modifications and their regulating enzymes in controlling the different stages of the autophagic process in cancer cells, and consider how the experimental modulation of tubulin-modifying enzymes influences the autophagic process in cancer cells and impacts on cancer cell survival and thereby represents a new and fruitful avenue in cancer therapy.