Dual Role of p73 in Cancer Microenvironment and DNA Damage Response
Julian M. Rozenberg,
Svetlana Zvereva,
Alexandra Dalina,
Igor Blatov,
Ilya Zubarev,
Daniil Luppov,
Alexander Bessmertnyi,
Alexander Romanishin,
Lamak Alsoulaiman,
Vadim Kumeiko,
Alexander Kagansky,
Gerry Melino,
Nikolai A. Barlev
Affiliations
Julian M. Rozenberg
Laboratory of Cell Signaling Regulation, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia
Svetlana Zvereva
Laboratory of Cell Signaling Regulation, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia
Alexandra Dalina
The Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
Igor Blatov
Laboratory of Cell Signaling Regulation, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia
Ilya Zubarev
Laboratory of Cell Signaling Regulation, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia
Daniil Luppov
Laboratory of Cell Signaling Regulation, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia
Alexander Bessmertnyi
Faculty of Computer Science, School of Software Engineering, Higher School of Economics University, 101000 Moscow, Russia
Alexander Romanishin
School of Life Sciences, Immanuel Kant Baltic Federal University, 236041 Kaliningrad, Russia
Lamak Alsoulaiman
Laboratory of Cell Signaling Regulation, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia
Vadim Kumeiko
School of Biomedicine, Far Eastern Federal University, 690091 Vladivostok, Russia
Alexander Kagansky
Laboratory of Cell Signaling Regulation, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia
Gerry Melino
Department of Medicine, University of Rome Tor Vergata, 00133 Roma, Italy
Nikolai A. Barlev
Laboratory of Cell Signaling Regulation, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia
Understanding the mechanisms that regulate cancer progression is pivotal for the development of new therapies. Although p53 is mutated in half of human cancers, its family member p73 is not. At the same time, isoforms of p73 are often overexpressed in cancers and p73 can overtake many p53 functions to kill abnormal cells. According to the latest studies, while p73 represses epithelial–mesenchymal transition and metastasis, it can also promote tumour growth by modulating crosstalk between cancer and immune cells in the tumor microenvironment, M2 macrophage polarisation, Th2 T-cell differentiation, and angiogenesis. Thus, p73 likely plays a dual role as a tumor suppressor by regulating apoptosis in response to genotoxic stress or as an oncoprotein by promoting the immunosuppressive environment and immune cell differentiation.
