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, epithelial-mesenchymal transition, metastasis formation, metabolic rewiring, and immune escape. BRAF^V600E, 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 interactio

SUBMITTER: Bellazzo A 

PROVIDER: S-EPMC11984274 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature