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. 2020 Mar 4;11(10):2887–2920. doi: 10.7150/jca.41324

Figure 5.

Figure 5

Depiction of the “coercion hypothesis”. Our manipulation, say as a transfected cDNA (the large black triangle in the cytoplasm of Cell A) or as a transgene or a gene-knockout on the chromosome 17 (black dot in Cell A), coerces the primary cell into incessantly replicating and manifesting transformed morphology or behavior, such as colony formation in agar. The relentless proliferation will eventually lead to spontaneous occurrence of the epigenetic (red dots on the DNA of chromosomes 8 and 22 in Cell B) or genetic (black dots on the DNA of chromosomes 8 and 22 in Cell C) alterations that establish immortality and autonomy, making the cell truly neoplastic in behavior. Continuous proliferation will also cause spontaneous occurrence of the epigenetic (small red triangles on the DNA of chromosomes 8 and 22 in Cell B) or genetic (small black triangles on the DNA of chromosomes 8 and 22 in Cell C) alterations that establish neoplastic morphology. This is to say that immortality and autonomy as “the behavior aspect” of neoplastic property, as well as “the morphology aspect” of neoplastic property, may sometimes be controlled separately by different sets of epigenetic or genetic alterations, i.e. different sets of “hits”. Moreover, the cell authentically transformed via epigenetic mechanisms (Cell B) may initially be reversible back to the normal, but later it will likely develop such genetic alterations that make the cell lose the reversibility and progress into the state of Cell C. If our manipulation is made in a controllable manner and is withdrawn early, the primary cell (Cell A) will no longer manifest the transformed morphology and behavior and will undergo senescent death (if the cell is in a culture dish) or both senescent death and apoptosis (if the cell is in a live animal). However, the truly transformed cells (Cells B and C) may retain their neoplastic properties sustained by the epigenetic or genetic alterations, unless some extrinsic factors (such as a chemical) cause the cells to circumvent or override the epigenetic or genetic alterations and make the cells reverse back to the normal state with or without retaining the alterations. In other words, neoplastic morphology and behavior incurred by our manipulation, an extrinsic factor, are inauthentic, but those caused intrinsic epigenetic or genetic alteration(s) are authentic.