Hexachlorobenzene triggers AhR translocation to the nucleus, c-Src activation and EGFR transactivation in rat liver

Activation of the Aryl Hydrocarbon Receptor Leads to Resistance to EGFR TKIs in Non–Small Cell Lung Cancer by Activating Src-mediated Bypass Signaling

“…Thus, Src also emerges as a therapeutic target to overcome resistance driven by AhR in NSCLC. Although others have also demonstrated that AhR ligands treatment enhance Src phosphorylation (46)(47)(48), our study provides a proof-of-principle insight into the molecular machinery responsible for Src activation. In our model, the binding of AhR protein to a ligand recruits cytosolic Src protein in a transcriptionally independent manner.…”

Src-mediated aryl hydrocarbon and epidermal growth factor receptor cross talk stimulates colon cancer cell proliferation

“…In rat liver and immune cells, AhR ligands including TCDD were shown to activate EGFR and mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinases (ERK)1/2 (23,32,34). Depending on the cell type examined, these actions of AhR cause pleiotropic effects: increased cell proliferation in some cells and enhanced apoptosis in others.…”

Integrated analysis of toxicity data of two pharmaceutical immunosuppressants and two environmental pollutants with immunomodulating properties to improve the understanding of side effects—A toxicopathologist׳s view

“…The analysis of both environmental pollutants, BaP and HCB considered only parameters connected to the immune system. The compounds are known to influence besides the immune system a variety of cells and organ systems mainly by interaction with the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) (Randi et al, 2008;Schraplau et al, 2015;Sparfel et al, 2010;Van Grevenynghe et al, 2005). The AHR can act variably on the immune system after binding with xenobiotics: on one side as a sensor with protective properties against deleterious changes such as inflammation but is on the other side in case of prolonged exposure associated with pathologic consequences like autoimmunity and tumor proliferation (Julliard et al, 2014).…”

“…For humans, the same CYP enzymes are responsible for this drug-metabolism (Martignoni et al, 2006). HCB is a weak agonist of the AHR and the predication that toxicity is mediated by AHR is restricted and inconclusive (Randi et al, 2008). The liver has been shown to be a main target organ of oral BAP in rats and mice (Uno et al, 2006).…”