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. 2016 Nov;8(11):E1528–E1531. doi: 10.21037/jtd.2016.11.59

Figure 1.

Figure 1

ZEB1 suppresses EGFR-mutant non-small cell lung cancer (NSCLC) tumorigenesis and mediates EGFR inhibitor resistance. In the discussed report ZEB1 was shown to inhibit EGFR-mutant NSCLC by repressing miR-200c expression, which subsequently allows for a target gene of miR-200c, NOTCH1, to repress ERBB3 expression. ZEB1 suppression of ERBB3 expression appears to be an important mechanism through which ZEB1 suppresses EGFR-mutant tumorigenesis. However, there may be additional miR-200c targets and potentially other ZEB1 targets that are important for the tumor suppressive role of ZEB1. Conversely, ZEB1 suppression of miR-200c expression and subsequent derepression of NOTCH1 was also shown to be required for ZEB1-mediated EGFR tyrosine kinase inhibitor resistance in NSCLC cell lines. Similar to the tumor suppressive function of ZEB1, ZEB1-mediated resistance most likely involves miR-200c targets, beyond NOTCH1, and may require additional ZEB1 target genes. Future studies are required to further delineate the mechanisms of ZEB1-mediated suppression of EGFR-mutant NSCLC and EGFR inhibitor resistance.