Dual Role of DUOX1-Derived Reactive Oxygen Species in Melanoma
Melanoma is the most serious type of skin cancer. Inflammation and oxidative stress play an essential role in the development of several types of cancer, including melanoma. Although oxidative stress promotes tumor growth, once cells escape from the primary tumor, they are subjected to a more hostil...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/3/708 |
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| author | Irene Pardo-Sánchez Sofía Ibañez-Molero Diana García-Moreno Victoriano Mulero |
| author_facet | Irene Pardo-Sánchez Sofía Ibañez-Molero Diana García-Moreno Victoriano Mulero |
| author_sort | Irene Pardo-Sánchez |
| collection | DOAJ |
| description | Melanoma is the most serious type of skin cancer. Inflammation and oxidative stress play an essential role in the development of several types of cancer, including melanoma. Although oxidative stress promotes tumor growth, once cells escape from the primary tumor, they are subjected to a more hostile environment, with higher levels of oxidative stress typically killing most cancer cells. As Dual Oxidase 1 (DUOX1) is a major producer of reactive oxygen species (ROS) in epithelia, we used allotransplantation and autochthonous melanoma models in zebrafish together with in silico analysis of the occurrence and relevance of <i>DUOX1</i> expression of the skin cutaneous melanoma (SKCM) cohort of The Cancer Genome Atlas (TCGA) to address the role of this enzyme in the aggressiveness of melanoma cells in vivo. It was found that high transcript levels of the gene encoding DUOX1 were associated with the poor prognosis of patients in the early-stage melanoma of TCGA cohort. However, <i>DUOX1</i> transcript levels were not found to be associated to the prognosis of late-stage SKCM patients. In addition, the transcript level of <i>DUOX1</i> in metastatic SKCM was lower than in primary SKCM. Using zebrafish primary melanoma and allotransplantation models, we interrogated the role of DUOX1 in vivo. Our results confirmed a dual role of DUOX1, which restrains melanoma proliferation but promotes metastasis. As this effect is only observed in immunocompromised individuals, the immune system appears to be able to counteract this elevated metastatic potential of DUOX1-deficient melanomas. |
| first_indexed | 2024-03-11T07:00:47Z |
| format | Article |
| id | doaj.art-a1268ea393f24f1fa36967fd9818fbeb |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T07:00:47Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-a1268ea393f24f1fa36967fd9818fbeb2023-11-17T09:18:40ZengMDPI AGAntioxidants2076-39212023-03-0112370810.3390/antiox12030708Dual Role of DUOX1-Derived Reactive Oxygen Species in MelanomaIrene Pardo-Sánchez0Sofía Ibañez-Molero1Diana García-Moreno2Victoriano Mulero3Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, SpainDepartamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, SpainInstituto Murciano de Investigación Biosanitaria (IMIB)-Pascual Parrilla, 30120 Murcia, SpainDepartamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, SpainMelanoma is the most serious type of skin cancer. Inflammation and oxidative stress play an essential role in the development of several types of cancer, including melanoma. Although oxidative stress promotes tumor growth, once cells escape from the primary tumor, they are subjected to a more hostile environment, with higher levels of oxidative stress typically killing most cancer cells. As Dual Oxidase 1 (DUOX1) is a major producer of reactive oxygen species (ROS) in epithelia, we used allotransplantation and autochthonous melanoma models in zebrafish together with in silico analysis of the occurrence and relevance of <i>DUOX1</i> expression of the skin cutaneous melanoma (SKCM) cohort of The Cancer Genome Atlas (TCGA) to address the role of this enzyme in the aggressiveness of melanoma cells in vivo. It was found that high transcript levels of the gene encoding DUOX1 were associated with the poor prognosis of patients in the early-stage melanoma of TCGA cohort. However, <i>DUOX1</i> transcript levels were not found to be associated to the prognosis of late-stage SKCM patients. In addition, the transcript level of <i>DUOX1</i> in metastatic SKCM was lower than in primary SKCM. Using zebrafish primary melanoma and allotransplantation models, we interrogated the role of DUOX1 in vivo. Our results confirmed a dual role of DUOX1, which restrains melanoma proliferation but promotes metastasis. As this effect is only observed in immunocompromised individuals, the immune system appears to be able to counteract this elevated metastatic potential of DUOX1-deficient melanomas.https://www.mdpi.com/2076-3921/12/3/708melanomaDUOX1oxidative stressreactive oxygen speciesmetastasiszebrafish |
| spellingShingle | Irene Pardo-Sánchez Sofía Ibañez-Molero Diana García-Moreno Victoriano Mulero Dual Role of DUOX1-Derived Reactive Oxygen Species in Melanoma Antioxidants melanoma DUOX1 oxidative stress reactive oxygen species metastasis zebrafish |
| title | Dual Role of DUOX1-Derived Reactive Oxygen Species in Melanoma |
| title_full | Dual Role of DUOX1-Derived Reactive Oxygen Species in Melanoma |
| title_fullStr | Dual Role of DUOX1-Derived Reactive Oxygen Species in Melanoma |
| title_full_unstemmed | Dual Role of DUOX1-Derived Reactive Oxygen Species in Melanoma |
| title_short | Dual Role of DUOX1-Derived Reactive Oxygen Species in Melanoma |
| title_sort | dual role of duox1 derived reactive oxygen species in melanoma |
| topic | melanoma DUOX1 oxidative stress reactive oxygen species metastasis zebrafish |
| url | https://www.mdpi.com/2076-3921/12/3/708 |
| work_keys_str_mv | AT irenepardosanchez dualroleofduox1derivedreactiveoxygenspeciesinmelanoma AT sofiaibanezmolero dualroleofduox1derivedreactiveoxygenspeciesinmelanoma AT dianagarciamoreno dualroleofduox1derivedreactiveoxygenspeciesinmelanoma AT victorianomulero dualroleofduox1derivedreactiveoxygenspeciesinmelanoma |