Fig 2: The expression of leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1), the repressor of epidermal growth factor receptor (EGFR), was up-regulated in AHR-KO clones. (A) Representative images and quantitative data showed the up-regulation of LRIG1 protein level in AHR-KO clones. Contrarily, the EGFR is expressed in the opposite manner of LRIG1. (B) By using immunoprecipitation assay, the protein complex comprising of AHR, EGFR, and LRIG1 was demonstrated in A549 wt. However, in AHR-KO clones, less EGFR was associated with LRIG1. (C) A short-term incubation with MG132 (10 µM; proteasome inhibitor) obviously boosted LRIG1 protein level in A549 and BEAS-2B, but without alternations on EGFR. These data suggest the interaction of LRIG1 to AHR might direct LRIG1 toward proteasome-dependent degradation. (** p < 0.01, *** p < 0.001, indicates statistically significant difference from the wild-type control).

Fig 3: LRIG1-mediated EGFR degradation may be a disintegrin and metalloprotease 17 (ADAM17)-dependent. (A) Representative images and quantitative histograms showed induction of ADAM17, a membrane-bound metalloproteinase, in AHR-KO clones of A549 and BEAS-2B. (B) After 1 h incubation with TAPI-2 (10 µM; ADAM17 inhibitor), the EGFR level was elevated obviously; however, the EGFR returned to degradation at 3 h, either in A549 AHR-KO or in BEAS-2B AHR-KO. These data suggest LRIG1-mediated EGFR degradation is ADAM17-dependent and is a continuously active process. (* p < 0.05, *** p < 0.001, indicates statistically significant difference from the wild-type control).