Fig. 2.
Tumor plasticity. EMP, dedifferentiation, transdifferentiation and cell fusion can be viewed as the four major sources of tumor plasticity and heterogeneity during tumorigenesis. EMP enhances invasion, and metastatic dissemination. Dedifferentiation of mature cells increases stemness and is believed to contribute to therapy resistance. Transdifferentiation causes one cell type to interconvert into a different cell type and cell fusion generates hybrid cells with both epithelial and immune cell-like properties. All process share some common characteristics and similar regulatory mechanisms. The three small circles represent the three major inducers of tumor-plasticity. Mutations in most important tumor suppressors and oncogenes, epigenetic modifications and the inflammatory microenvironment are the most potent inducers of tumor cell plasticity.