Dualistic role of ZEB1 and ZEB2 in tumor progression
Parfenyev S.E. Daks A.A. Shuvalov O.Y. Fedorova O.A. Pestov N.B. Korneenko T.V. Barlev N.A.
December 2025BioMed Central Ltd
Biology Direct
2025#20Issue 1
It is generally accepted that ZEB1 and ZEB2 act as master regulators of the epithelial-mesenchymal transition, which arguably is the key mechanism of metastasis. Accordingly, they are deemed as negative predictors of the survival of cancer patients by promoting the emergence of secondary foci of the disease. Paradoxically, in some types of cancer types the opposite effect is observed, i.e. ZEB1 and ZEB2 are associated with better prognosis for cancer patients. In this review, we discuss the hypothesis that the tumorigenic effects of ZEB1/ZEB2 can be different in various tissues depending on the initial status of these proteins in the corresponding healthy tissues. Emerging evidence suggests that ZEB1 and ZEB2 are constitutively expressed in several healthy tissues, performing vital functions. Consequently, reducing the expression of ZEB1 and ZEB2 could negatively affect these tissues causing various diseases, including cancer. Finally, the dualistic role of ZEB1 and ZEB2 as immune modulators and their effect on tumor microenvironment is also discussed.
Cancer , Carcinogenesis , Epithelial-mesenchymal transition , ZEB1, ZEB2
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Laboratory of Gene Expression Regulation, Institute of Cytology RAS, Saint-Petersburg, 164064, Russian Federation
Vavilov Institute of General Genetics, Moscow, 119991, Russian Federation
Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides, Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products, Moscow, 108819, Russian Federation
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russian Federation
Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana, 01000, Kazakhstan
Laboratory of Gene Expression Regulation
Vavilov Institute of General Genetics
Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
Department of Biomedical Sciences
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