The Role of the Metabolism of Zinc and Manganese Ions in Human Cancerogenesis
Julian Markovich Rozenberg,
Margarita Kamynina,
Maksim Sorokin,
Marianna Zolotovskaia,
Elena Koroleva,
Kristina Kremenchutckaya,
Alexander Gudkov,
Anton Buzdin,
Nicolas Borisov
Affiliations
Julian Markovich Rozenberg
Moscow Institute of Physics and Technology, National Research University, 141700 Moscow, Russia
Margarita Kamynina
Group of Experimental Biotherapy and Diagnostic, Institute for Regenerative Medicine, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia
Maksim Sorokin
Moscow Institute of Physics and Technology, National Research University, 141700 Moscow, Russia
Marianna Zolotovskaia
Moscow Institute of Physics and Technology, National Research University, 141700 Moscow, Russia
Elena Koroleva
Moscow Institute of Physics and Technology, National Research University, 141700 Moscow, Russia
Kristina Kremenchutckaya
Moscow Institute of Physics and Technology, National Research University, 141700 Moscow, Russia
Alexander Gudkov
Group of Experimental Biotherapy and Diagnostic, Institute for Regenerative Medicine, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia
Anton Buzdin
Moscow Institute of Physics and Technology, National Research University, 141700 Moscow, Russia
Nicolas Borisov
Moscow Institute of Physics and Technology, National Research University, 141700 Moscow, Russia
Metal ion homeostasis is fundamental for life. Specifically, transition metals iron, manganese and zinc play a pivotal role in mitochondrial metabolism and energy generation, anti-oxidation defense, transcriptional regulation and the immune response. The misregulation of expression or mutations in ion carriers and the corresponding changes in Mn2+ and Zn2+ levels suggest that these ions play a pivotal role in cancer progression. Moreover, coordinated changes in Mn2+ and Zn2+ ion carriers have been detected, suggesting that particular mechanisms influenced by both ions might be required for the growth of cancer cells, metastasis and immune evasion. Here, we present a review of zinc and manganese pathophysiology suggesting that these ions might cooperatively regulate cancerogenesis. Zn and Mn effects converge on mitochondria-induced apoptosis, transcriptional regulation and the cGAS-STING signaling pathway, mediating the immune response. Both Zn and Mn influence cancer progression and impact treatment efficacy in animal models and clinical trials. We predict that novel strategies targeting the regulation of both Zn and Mn in cancer will complement current therapeutic strategies.
