Unraveling the role of hypoxia-inducible factors in cutaneous melanoma: from mechanisms to therapeutic opportunities
Abstract Hypoxia is a common feature of solid malignancies, including cutaneous melanoma (CM). Hypoxia-inducible factor (HIF)-1α and HIF-2α orchestrate cellular responses to hypoxia and coordinate a transcriptional program that promote several aggressive features in CM, such as angiogenesis, epithel...
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| Format: | Article |
| Language: | English |
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BMC
2025-04-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02173-4 |
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| author | Arianna Bellazzo Barbara Montico Roberto Guerrieri Francesca Colizzi Agostino Steffan Jerry Polesel Elisabetta Fratta |
| author_facet | Arianna Bellazzo Barbara Montico Roberto Guerrieri Francesca Colizzi Agostino Steffan Jerry Polesel Elisabetta Fratta |
| author_sort | Arianna Bellazzo |
| collection | DOAJ |
| description | Abstract Hypoxia is a common feature of solid malignancies, including cutaneous melanoma (CM). Hypoxia-inducible factor (HIF)-1α and HIF-2α orchestrate cellular responses to hypoxia and coordinate a transcriptional program that promote several aggressive features in CM, such as angiogenesis, epithelial-mesenchymal transition, metastasis formation, metabolic rewiring, and immune escape. BRAFV600E, which is the most frequent mutation observed in CM patients, usually increases HIF-α signaling not only in hypoxia, but also in normoxic CM cells, enabling HIF-1α and HIF-2α to continuously activate downstream molecular pathways. In this review, we aim to provide a comprehensive overview of the intricate role and regulation of HIF-1α and HIF-2α in CM, with a brief focus on the complex interactions between HIF-α subunits and non-coding RNAs. We also discuss HIF-α-mediated cellular responses in normoxia along with the mechanisms that allow HIF-α subunits to maintain their stability under normal oxygen conditions. Finally, we resume available evidence on potential therapeutic approaches aimed at targeting HIF-1α and/or HIF-2α. |
| format | Article |
| id | doaj-art-b16656bc751b48ca98fc41cdf2ac8390 |
| institution | OA Journals |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-b16656bc751b48ca98fc41cdf2ac83902025-08-20T02:11:47ZengBMCCell Communication and Signaling1478-811X2025-04-0123111910.1186/s12964-025-02173-4Unraveling the role of hypoxia-inducible factors in cutaneous melanoma: from mechanisms to therapeutic opportunitiesArianna Bellazzo0Barbara Montico1Roberto Guerrieri2Francesca Colizzi3Agostino Steffan4Jerry Polesel5Elisabetta Fratta6Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCSImmunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCSImmunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCSImmunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCSImmunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCSUnit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCSImmunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCSAbstract Hypoxia is a common feature of solid malignancies, including cutaneous melanoma (CM). Hypoxia-inducible factor (HIF)-1α and HIF-2α orchestrate cellular responses to hypoxia and coordinate a transcriptional program that promote several aggressive features in CM, such as angiogenesis, epithelial-mesenchymal transition, metastasis formation, metabolic rewiring, and immune escape. BRAFV600E, which is the most frequent mutation observed in CM patients, usually increases HIF-α signaling not only in hypoxia, but also in normoxic CM cells, enabling HIF-1α and HIF-2α to continuously activate downstream molecular pathways. In this review, we aim to provide a comprehensive overview of the intricate role and regulation of HIF-1α and HIF-2α in CM, with a brief focus on the complex interactions between HIF-α subunits and non-coding RNAs. We also discuss HIF-α-mediated cellular responses in normoxia along with the mechanisms that allow HIF-α subunits to maintain their stability under normal oxygen conditions. Finally, we resume available evidence on potential therapeutic approaches aimed at targeting HIF-1α and/or HIF-2α.https://doi.org/10.1186/s12964-025-02173-4Cutaneous melanomaHypoxia-inducible factorsHypoxiaNormoxiaNon-coding RNAs |
| spellingShingle | Arianna Bellazzo Barbara Montico Roberto Guerrieri Francesca Colizzi Agostino Steffan Jerry Polesel Elisabetta Fratta Unraveling the role of hypoxia-inducible factors in cutaneous melanoma: from mechanisms to therapeutic opportunities Cell Communication and Signaling Cutaneous melanoma Hypoxia-inducible factors Hypoxia Normoxia Non-coding RNAs |
| title | Unraveling the role of hypoxia-inducible factors in cutaneous melanoma: from mechanisms to therapeutic opportunities |
| title_full | Unraveling the role of hypoxia-inducible factors in cutaneous melanoma: from mechanisms to therapeutic opportunities |
| title_fullStr | Unraveling the role of hypoxia-inducible factors in cutaneous melanoma: from mechanisms to therapeutic opportunities |
| title_full_unstemmed | Unraveling the role of hypoxia-inducible factors in cutaneous melanoma: from mechanisms to therapeutic opportunities |
| title_short | Unraveling the role of hypoxia-inducible factors in cutaneous melanoma: from mechanisms to therapeutic opportunities |
| title_sort | unraveling the role of hypoxia inducible factors in cutaneous melanoma from mechanisms to therapeutic opportunities |
| topic | Cutaneous melanoma Hypoxia-inducible factors Hypoxia Normoxia Non-coding RNAs |
| url | https://doi.org/10.1186/s12964-025-02173-4 |
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