Role of Ubiquitination and Epigenetics in the Regulation of AhR Signaling in Carcinogenesis and Metastasis: “Albatross around the Neck” or “Blessing in Disguise”
The molecular mechanisms and signal transduction cascades evoked by the activation of aryl hydrocarbon receptor (AhR) are becoming increasingly understandable. AhR is a ligand-activated transcriptional factor that integrates environmental, dietary and metabolic cues for the pleiotropic regulation of...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/19/2382 |
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| author | Ammad Ahmad Farooqi Venera Rakhmetova Gulnara Kapanova Gulnur Tanbayeva Akmaral Mussakhanova Akmaral Abdykulova Alma-Gul Ryskulova |
| author_facet | Ammad Ahmad Farooqi Venera Rakhmetova Gulnara Kapanova Gulnur Tanbayeva Akmaral Mussakhanova Akmaral Abdykulova Alma-Gul Ryskulova |
| author_sort | Ammad Ahmad Farooqi |
| collection | DOAJ |
| description | The molecular mechanisms and signal transduction cascades evoked by the activation of aryl hydrocarbon receptor (AhR) are becoming increasingly understandable. AhR is a ligand-activated transcriptional factor that integrates environmental, dietary and metabolic cues for the pleiotropic regulation of a wide variety of mechanisms. AhR mediates transcriptional programming in a ligand-specific, context-specific and cell-type-specific manner. Pioneering cutting-edge research works have provided fascinating new insights into the mechanistic role of AhR-driven downstream signaling in a wide variety of cancers. AhR ligands derived from food, environmental contaminants and intestinal microbiota strategically activated AhR signaling and regulated multiple stages of cancer. Although AhR has classically been viewed and characterized as a ligand-regulated transcriptional factor, its role as a ubiquitin ligase is fascinating. Accordingly, recent evidence has paradigmatically shifted our understanding and urged researchers to drill down deep into these novel and clinically valuable facets of AhR biology. Our rapidly increasing realization related to AhR-mediated regulation of the ubiquitination and proteasomal degradation of different proteins has started to scratch the surface of intriguing mechanisms. Furthermore, AhR and epigenome dynamics have shown previously unprecedented complexity during multiple stages of cancer progression. AhR not only transcriptionally regulated epigenetic-associated molecules, but also worked with epigenetic-modifying enzymes during cancer progression. In this review, we have summarized the findings obtained not only from cell-culture studies, but also from animal models. Different clinical trials are currently being conducted using AhR inhibitors and PD-1 inhibitors (Pembrolizumab and nivolumab), which confirm the linchpin role of AhR-related mechanistic details in cancer progression. Therefore, further studies are required to develop a better comprehension of the many-sided and “diametrically opposed” roles of AhR in the regulation of carcinogenesis and metastatic spread of cancer cells to the secondary organs. |
| first_indexed | 2024-03-10T21:48:02Z |
| format | Article |
| id | doaj.art-d3d9cb5f056643d5b1dd1c122ce10265 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T21:48:02Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d3d9cb5f056643d5b1dd1c122ce102652023-11-19T14:13:01ZengMDPI AGCells2073-44092023-09-011219238210.3390/cells12192382Role of Ubiquitination and Epigenetics in the Regulation of AhR Signaling in Carcinogenesis and Metastasis: “Albatross around the Neck” or “Blessing in Disguise”Ammad Ahmad Farooqi0Venera Rakhmetova1Gulnara Kapanova2Gulnur Tanbayeva3Akmaral Mussakhanova4Akmaral Abdykulova5Alma-Gul Ryskulova6Institute of Biomedical and Genetic Engineering (IBGE), Islamabad 54000, PakistanDepartment of Internal Diseases, Medical University of Astana, Astana 010000, KazakhstanFaculty of Medicine and healthcare, Al-Farabi Kazakh National University, 71 Al-Farabi Ave, Almaty 050040, KazakhstanFaculty of Medicine and healthcare, Al-Farabi Kazakh National University, 71 Al-Farabi Ave, Almaty 050040, KazakhstanDepartment of Public Health and Management, Astana Medical University, Astana 010000, KazakhstanDepartment of General Medical Practice, General Medicine Faculty, Asfendiyarov Kazakh National Medical University, Almaty 050000, KazakhstanDepartment of Public Health and Social Sciences, Kazakhstan Medical University “KSPH”, Utenos Str. 19A, Almaty 050060, KazakhstanThe molecular mechanisms and signal transduction cascades evoked by the activation of aryl hydrocarbon receptor (AhR) are becoming increasingly understandable. AhR is a ligand-activated transcriptional factor that integrates environmental, dietary and metabolic cues for the pleiotropic regulation of a wide variety of mechanisms. AhR mediates transcriptional programming in a ligand-specific, context-specific and cell-type-specific manner. Pioneering cutting-edge research works have provided fascinating new insights into the mechanistic role of AhR-driven downstream signaling in a wide variety of cancers. AhR ligands derived from food, environmental contaminants and intestinal microbiota strategically activated AhR signaling and regulated multiple stages of cancer. Although AhR has classically been viewed and characterized as a ligand-regulated transcriptional factor, its role as a ubiquitin ligase is fascinating. Accordingly, recent evidence has paradigmatically shifted our understanding and urged researchers to drill down deep into these novel and clinically valuable facets of AhR biology. Our rapidly increasing realization related to AhR-mediated regulation of the ubiquitination and proteasomal degradation of different proteins has started to scratch the surface of intriguing mechanisms. Furthermore, AhR and epigenome dynamics have shown previously unprecedented complexity during multiple stages of cancer progression. AhR not only transcriptionally regulated epigenetic-associated molecules, but also worked with epigenetic-modifying enzymes during cancer progression. In this review, we have summarized the findings obtained not only from cell-culture studies, but also from animal models. Different clinical trials are currently being conducted using AhR inhibitors and PD-1 inhibitors (Pembrolizumab and nivolumab), which confirm the linchpin role of AhR-related mechanistic details in cancer progression. Therefore, further studies are required to develop a better comprehension of the many-sided and “diametrically opposed” roles of AhR in the regulation of carcinogenesis and metastatic spread of cancer cells to the secondary organs.https://www.mdpi.com/2073-4409/12/19/2382cancerapoptosissignalingxenografted micepreclinical trials |
| spellingShingle | Ammad Ahmad Farooqi Venera Rakhmetova Gulnara Kapanova Gulnur Tanbayeva Akmaral Mussakhanova Akmaral Abdykulova Alma-Gul Ryskulova Role of Ubiquitination and Epigenetics in the Regulation of AhR Signaling in Carcinogenesis and Metastasis: “Albatross around the Neck” or “Blessing in Disguise” Cells cancer apoptosis signaling xenografted mice preclinical trials |
| title | Role of Ubiquitination and Epigenetics in the Regulation of AhR Signaling in Carcinogenesis and Metastasis: “Albatross around the Neck” or “Blessing in Disguise” |
| title_full | Role of Ubiquitination and Epigenetics in the Regulation of AhR Signaling in Carcinogenesis and Metastasis: “Albatross around the Neck” or “Blessing in Disguise” |
| title_fullStr | Role of Ubiquitination and Epigenetics in the Regulation of AhR Signaling in Carcinogenesis and Metastasis: “Albatross around the Neck” or “Blessing in Disguise” |
| title_full_unstemmed | Role of Ubiquitination and Epigenetics in the Regulation of AhR Signaling in Carcinogenesis and Metastasis: “Albatross around the Neck” or “Blessing in Disguise” |
| title_short | Role of Ubiquitination and Epigenetics in the Regulation of AhR Signaling in Carcinogenesis and Metastasis: “Albatross around the Neck” or “Blessing in Disguise” |
| title_sort | role of ubiquitination and epigenetics in the regulation of ahr signaling in carcinogenesis and metastasis albatross around the neck or blessing in disguise |
| topic | cancer apoptosis signaling xenografted mice preclinical trials |
| url | https://www.mdpi.com/2073-4409/12/19/2382 |
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