Host: The Japanese Pharmacological Society
Name : The 95th Annual Meeting of the Japanese Pharmacological Society
Number : 95
Location : Fukuoka
Date : March 07, 2022 - March 09, 2022
Epidermal growth factor receptor (EGFR) is most intensively studied receptor tyrosine kinase. Several EGFR mutations and modifications have been known to induce abnormal self-activation, which plays a central role in carcinogenesis. Environmental air pollutants, which are associated with cancer and respiratory diseases, can also activate EGFR. For example, the environmental electrophile 1,2-naphthoquinone (1,2-NQ) has previously been shown to impact EGFR signaling. Humans are exposed to NQs through combustion of fossil and diesel fuel and from tobacco smoke. In addition, 1,2-NQ was recently detected in atmospheric PM2.5.
In this symposium, we will present that 1,2-NQ is a novel activator of EGFR but not other types of EGFR family proteins. We found that 1,2-NQ forms a covalent bond with Lys80 located in extracellular domain I of EGFR. This modification leads to the activation of EGFR-Akt signaling in a human lung adenocarcinoma cell line. Our study reveals a novel mode of EGFR pathway activation and suggests a link between abnormal EGFR activation and environmental pollutant-associated diseases such as cancer.
