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. 2016 Jan 19;7(7):8184–8199. doi: 10.18632/oncotarget.6945

Figure 6. A schematic model of the p38 MAPK/p53/EGFR pathway that leads to PTX resistance.

Figure 6

Schematic diagram for the proposed model of the PTX resistance in NSCLC cells. Continuous exposure of cancer cells to PTX activates a stress-induced kinase p38 MAPK to develop PTX resistance. In chemo-naïve cells, p53 is generally degraded by its E3 ligase, MDM2, conferring the high sensitivity to PTX. However, the constitutively activated p38 MAPK in PTX-resistant cells induces the rapid degradation of MDM2 through the classical ubiquitin-proteasome pathway and the consequent stabilization of p53. The stabilized p53 translocates to the nucleus and regulates the expression of its target genes, including EGFR, which finally leads to the generation of acquired resistance to PTX.