Abstract
Zinc has been suggested to play a role in carcinogenesis and tumor progression. Serum zinc levels of lung cancer patients are for example lower than in healthy individuals. The activation and expression of the epidermal growth factor receptor (EGFR), which plays a role in tumor biology, are presumably influenced by zinc. EGFR activation influences cell adhesion and immune escape. This study provides insights into the impacts of zinc on the EGFR activation and expression of downstream proteins such as E-cadherin and PD-L1 in the alveolar carcinoma cell line A549. To model chronic changes in zinc homeostasis, A549 cells were cultured in media with different zinc contents. EGFR surface expression of unstimulated and stimulated A549 cells was determined by flow cytometry. EGFR phosphorylation as well as the protein expression of E-cadherin and PD-L1 were analyzed by Western blot. In our hands, chronic zinc deficiency led to increased EGFR surface expression, decreased E-cadherin protein expression and increased PD-L1 protein expression. Zinc supplementation decreased EGFR surface expression and PD-L1 protein expression. In summary, zinc-deficient A549 cells may display a more malignant phenotype. Thus, future clinical research should further focus on the possible benefits of restoring disturbed zinc homeostasis, especially in lung cancer patients.
Highlights
Zinc is an essential trace element involved in various cellular processes such as DNA repair, receptor-induced signaling and enzyme stability
To extend ourTo previous we modeled thegrowth epidermal growth factor receptor extend findings, our previous findings,chronic we changes in zincchanges homeostasis and included zinc as well as zinc deficiency modeled chronic in zinc homeostasis andsupplementation included zinc supplementation as well in the study presented here
As the decrease in E-cadherin is a prominent feature among EMT, our results suggest that zinc deficiency may promote events that result in EMT
Summary
Zinc is an essential trace element involved in various cellular processes such as DNA repair, receptor-induced signaling and enzyme stability. Zinc deficiency can occur due to chronic inflammation and malnutrition, among others, and bears many health risks. These include a decreased sense of smell and taste, delayed wound healing, growth retardation and various chronic diseases [1,2,3,4]. A role in carcinogenesis was attributed to zinc deficiency [1,5,6,7,8,9,10]. The differential expression of certain zinc transporting proteins was associated with cancer [15,16,17]. The role of zinc in cancer development and progression is complex and needs to be further explored
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have