1. Figure 5 The mechanism underlying epithelial-to-mesenchymal
transition (EMT)-dependent acquisition of therapeutic resistance
Figure 5 | The mechanism underlying epithelial-to-mesenchymal transition (EMT)-dependent acquisition of therapeutic resistance. a | EMT-associated downregulation of multiple apoptotic signalling pathways, enhanced drug efflux, and slow cell proliferation all contribute to enhance the general resistance of carcinoma cells to anticancer drugs. b | In addition, the EMT- associated transcription factor Snail induces the expression of the AXL receptor tyrosine kinase on the surface of carcinoma cells. AXL signalling, triggered by the binding of its ligand growth arrest-specific protein 6 (GAS6), enables Snail-expressing carcinoma cells to override cytostatic effects of EGFR blockade with small-molecule inhibitors (such as erlotinib) or antagonistic monoclonal antibodies. c | The EMT programme also activates several processes that enable carcinoma cells to evade the lethal effect of cytotoxic T cells. These changes include elevated expression of programmed cell death 1 ligand 1 (PD-L1), which binds to the programmed cell death protein 1 (PD-1) inhibitory immune-checkpoint receptor that is expressed by cytotoxic T cells and thereby diminishes their function; and increased secretion of thrombospondin-1 (TSP-1), which promotes the development of regulatory T cells within the tumour microenvironment that ultimately suppress the activity of cytotoxic T cells.
Shibue, T. & Weinberg, R. A. (2017) EMT, CSCs, and drug resistance: the mechanistic link and clinical implications
Nat. Rev. Clin. Oncol. doi: /nrclinonc