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Oxidative stress and cancer heterogeneity orchestrate NRF2 roles relevant for therapy response

Gall Trošelj, Koraljka; Tomljanović, Marko; Jaganjac, Morana; Matijević Glavan, Tanja; Čipak Gašparović, Ana; Milković, Lidija; Borović Šunjić, Suzana; Buttari, Brigitta; Profumo, Elisabetta; Saha, Sarmistha; Saso, Luciano; Žarković, Neven (2022) Oxidative stress and cancer heterogeneity orchestrate NRF2 roles relevant for therapy response. Molecules, 27 (5). ISSN 1420-3049

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Oxidative stress and its end-products, such as 4-hydroxynonenal (HNE), initiate activation of the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2)/Kelch Like ECH Associated Protein 1 (KEAP1) signaling pathway that plays a crucial role in the maintenance of cellular redox homeostasis. However, an involvement of 4-HNE and NRF2 in processes associated with the initiation of cancer, its progression, and response to therapy includes numerous, highly complex events. They occur through interactions between cancer and stromal cells. These events are dependent on many cell-type specific features. They start with the extent of NRF2 binding to its cytoplasmic repressor, KEAP1, and extend to the permissiveness of chromatin for transcription of Antioxidant Response Element (ARE)-containing genes that are NRF2 targets. This review will explore epigenetic molecular mechanisms of NRF2 transcription through the specific molecular anatomy of its promoter. It will explain the role of NRF2 in cancer stem cells, with respect to cancer therapy resistance. Additionally, it also discusses NRF2 involvement at the cross-roads of communication between tumor associated inflammatory and stromal cells, which is also an important factor involved in the response to therapy.

Item Type: Article
Uncontrolled Keywords: 4-hydroxynonenal; therapy resistance; cancer stem cells; tumor associated macrophages (TAMs); tumor associated neutrophils (TANs); polarization; NFE2L2 promoter; KEAP-1; micro RNA
Subjects: BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions: Division of Molecular Medicine
Depositing User: Kristina Ciglar
Date Deposited: 05 Apr 2022 13:07
DOI: 10.3390/molecules27051468

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