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Figure 2. Malignant and Senescent Epithelial Cells Contribute to Metastasis. A: malignant cells respond to TME cytokines or intrinsic genetic alterations in order to drive E-M/CSC plasticity, resulting in greater metastasis, enhanced disease recurrence, and therapeutic resistance; B: pre-malignant cells undergo senescence in response to aberrant oncogene or cytokine signaling. However, in some instances a small population of senescent cells may undergo E-M/CSC plasticity, and thus escape the tumor suppressive barrier of senescence and further contribute to the metastatic phenotype