Cell Fate in Cancer

The cell is the basic unit of life. The attainment of a nucleus to house the genetic material is thought to have provided a distinct advantage to the evolving cell, ultimately allowing the emergence of differentiated, specialized cells.  Hoarding evidence suggests that genomes are organized non-randomly into complex 3D configurations that vary according to cell type, stage of development, differentiation and disease status. The principles, which guide higher order organization, the mechanisms responsible for establishment, maintenance and alterations of higher order genome, and the functional consequences of aberrant genome and nuclear organization, have become zones of intense interest. The higher-order spatial and temporal organization of genomes in the cell nucleus is rapidly evolving as a driver of biological function in differentiation, development and disease and the incorporation of information on higher order genome organization add an additional level of complexity in our understanding of genome regulation.  DNA sequence variations and biochemical sequence modifications co-define cell fate. Through exploration of cancer genomes, new gene categories have been identified that imply novel underlying mechanisms related to epigenetics, transcriptional processes and cell differentiation. These contrivances are of major prominence in tumorigenesis and cancer therapy failure.

Differentiated tumor cells may present different elevated cell potencies. Thus, tumor heterogeneity may be presented as a certain three-dimensional space that is defined by the range of three key features – cell potency, cell lineage specificity and variance. Cell fate dynamics and the resulting cell population diversity and evolution during tumorigenesis and cancer drug treatment have been correlated with cellular responses to environmental stress. This might provide new insights for understanding tumorigenesis and new strategies that target whole cell system dynamics for cancer therapy.

The determination of a cell to a particular fate can be broken down into two states where the cell can be specified or determined. In the state of being committed or specified, the cell type is not yet determined and any bias the cell has toward a certain fate can be reversed or transformed to another fate. If a cell is in a determined state, the cell’s fate cannot be reversed or transformed. In general, this means that a cell determined to differentiate into a brain cell cannot be transformed into a skin cell. Determination is followed by differentiation, the actual changes in biochemistry, structure, and function that result in specific cell types. Differentiation often involves a change in appearance as well as function.

The fate of a cell describes what it will become in the course of normal development. The fate of a particular cell can be discovered by labeling that cell and observing what structures it becomes a part of. When the fate of all cells of an embryo has been discovered, we can build a fate map, which is a diagram of that organism at an early stage of development that indicates the fate of each cell or region at a later stage of development.

In development, epigenetics plays a central role. Epigenetics temporally regulates numerous genes to govern developmental decisions during lineage commitment. When a terminally differentiated somatic cell lineage is established, the cellular type and its features will be stably maintained by epigenetic marks. For a long time, this developmental process was regarded as irreversible. However, recent advances, inducing differentiated somatic cells to a pluripotent state, demonstrate that cells possess high plasticity of cell fate. Epigenetic mechanisms are responsible for reprogramming cell fate. Cancer cells present, to different extents, dedifferentiation states. From the angle of cell fate, cancers can be regarded as dysregulated (or dysfunctional) with respect to cell differentiation and, thus, they are at abnormal differentiation stages. Recently, the similarity of principles and mechanisms between cellular reprogramming and oncogenic transformation has been highlighted.

  • Oncoproteins and Cellular Targets
  • Emerging Concepts and Technologies
  • Genomics, Biomarkers and clinical trials
  • Integrative Science and Translation

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