The Role of Cellular Plasticity in Cancer Development

Abstract

It has traditionally been accepted that, in the process of cellular differentiation, developmental options are progressively restricted until commitment to a specific fate is established and then only terminal differentiation along this lineage is possible. Although this is usually the case in normal physiological development, the latest experimental evidences indicate that the differentiated state of mature cells is not always as stable and durable as it was thought to be. In fact, recently, a hidden plasticity has been revealed in differentiated cells which allows them to deviate to other cell types that might be, functionally, very far away in other developmental pathways. This plasticity has biological significance since it is necessary for normal development to occur, but it also makes possible the emergence of aberrant lineages when interferences with the normal transcriptional and epigenetic mechanisms in charge of maintaining cellular identity do appear. Cancer is one of the possible outcomes of this aberrant reprogramming. The plasticity of the initial cell suffering the first oncogenic alteration plays an essential role in cancer development, since only if this cell possesses enough plasticity a tumoral reprogramming will be possible and a full-blown tumor will develop. Also, plasticity makes it possible for differentiated cells to acquire cancer stem cell properties in the presence of the appropriate oncogenic insults. In this review we discuss the role of cellular plasticity in the normal development of adult tissues and how cellular susceptibility to reprogramming plays an essential part in cancer development.

Phenotypic Reversion of Invasive Neurofibromin-Deficient Schwannoma by FTS: Ras Inhibition Reduces BMP4/Erk/Smad Signaling

“…Phenotypic alterations and dedifferentiation of cancer cells are critical in malignancy and increase the invasive/ metastatic attributes of tumors (1). Chronically active Ras drives tumor progression through deregulation of proliferation and phenotypic transformation (2).…”

Stem cells, the current state of researches on this problem and the main directions of their development. From theory to clinical practice

“…Имеются определенные указания на то, что при-менение СК взрослых может готовить почву для ту-морогенеза [27,28].…”

The Dark Side of Cellular Plasticity: Stem Cells in Development and Cancer

“…Many of these findings have been driven by the postulation and final coming of age of the theory of the cancer stem cells (CSCs). It is beyond of the scope of this chapter to detail all the aspects and implications of this theory, which have been previously discussed to great extent Cobaleda and Sanchez-Garcia, 2009;Lobo et al, 2007;Reya et al, 2001;Sanchez-Garcia et al, 2007;Vicente-Duenas et al, 2009a), so here we will limit our discussion to the aspects related to cellular plasticity and differentiation. The CSC theory proposes that tumours are heterogeneous tissues, maintained by tissuespecific stem cells, in a manner very similar to any other stem cell-based tissue in the organism.…”

“…We group both concepts under the same umbrella (plasticity) since it is increasingly clear that the same mechanisms involved in stem cell competence during normal development are involved in the plasticity of more differentiated types of cells, not only in pathological conditions like tumorigenesis, but also in experimentally-induced fate-changing processes. In the last years, many advances have been made in our understanding of the biology of cellular plasticity (Graf and Enver, 2009;Gurdon and Melton, 2008;Hochedlinger and Jaenisch, 2006;Vicente-Duenas et al, 2009a). However, the molecular bases of stem cell competence (i.e.…”