Cancer, one of the most mortal diseases worldwide, is characterized by the gain of specific features and cellular heterogeneity. Clonal evolution is an established theory to explain heterogeneity, but the discovery of cancer stem cells expanded the concept to include the hierarchical growth and plasticity of cancer cells. The activation of epithelial-to-mesenchymal transition and its molecular players are widely correlated with the presence of cancer stem cells in tumors. Moreover, the acquisition of certain oncological features may be partially attributed to alterations in the levels, location or function of nucleolin, a multifunctional protein involved in several cellular processes. This review aims at integrating the established hallmarks of cancer with the plasticity of cancer cells as an emerging hallmark; responsible for tumor heterogeneity; therapy resistance and relapse. The discussion will contextualize the involvement of nucleolin in the establishment of cancer hallmarks and its application as a marker protein for targeted anticancer therapies.
Keywords: cancer stem cells; drug resistance; epithelial-to-mesenchymal transition; nucleolin; targeted therapies; tumor heterogeneity.