Abstract
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
Highlights
Cancer incidence is increasing and has become one of the leading causes of death and morbidity worldwide [1]
Cell plasticity represents another piece of complexity, which relates with the ability to transit between a stem-like phenotype and a more differentiated state, or vice-versa [7]. Such property is present in cancer stem cells (CSCs), in a process mediated by the epithelial-to-mesenchymal transition [8]
CSC are defined as a population of cells within the tumor microenvironment that are able to self-renew for self-maintenance of the population, and to differentiate into every tumor cell type, sustaining malignant growth [23]
Summary
Cancer incidence is increasing and has become one of the leading causes of death and morbidity worldwide [1]. The identification of tumor cells with stem-like features—the cancer stem cells (CSCs)—has introduced a new level of complexity, shifting the understanding on tumor growth and development from the purely clonal expansion towards a hierarchical organization of cancer cells [6] Cell plasticity represents another piece of complexity, which relates with the ability to transit between a stem-like phenotype and a more differentiated state, or vice-versa [7]. In this respect, nucleolin, a nucleolar protein, has several identified roles in essential intracellular pathways including transcription and translation, cell cycle and division, cell survival and differentiation [10]. An overview of already established hallmarks of cancer will be performed in the context of emerging ones: stemness and plasticity of cancer cells In this respect, the involvement of nucleolin in processes whose dysregulation leads to cancer hallmarks, including CSC-associated processes, will be discussed and further integrated in its application as a target for anticancer therapies
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