Tumorigenic Cell Reprogramming and Cancer Plasticity: Interplay between Signaling, Microenvironment, and Epigenetics

Figure 1

Cellular origin and mechanisms dictating the emergence of CSCs. (a) Cells with different positions in the tissue hierarchy can serve as the cell of origin (CO). Combination of epigenetic and genetic alterations can drive cell reprogramming and the direct onset of a CSC phenotype. In an alternative process, the CO can initiate tumorigenesis, without acquiring stem cell features, and acquisition of further oncogenic aberrations in a cell of the neoplastic progeny may drive CSC formation. CSCs are uniquely responsible for tumor progression and maintenance. (b) A combination of cell autonomous and noncell autonomous factors influence CSC formation and tumor development. Oncogenic mutation of stemness signaling can cause their hyperactivation independently from the tumor microenvironment (TME). Altered signaling from the TME, such as chronic inflammation, or signals from the stem cell niche can induce tumorigenic cell reprogramming. Different signaling converge to regulate epithelial-to-mesenchymal transition (EMT) in tumor initiation and progression.

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