Adherent-to-suspension transition promotes melanoma metastatic dissemination

Abstract

Melanoma is a highly metastatic skin cancer that often evades current therapeutic strategies primarily because of the complex mechanisms involved in metastasis. This study investigated the role of adherent-to-suspension transition (AST) in melanoma and its potential to facilitate metastasis by reprogramming cellular anchorage dependency. Using melanoma models, we demonstrated that the AST factors IKZF1, IRF8, and NFE2 are crucial for reprogramming, influencing gene expression related to cell adhesion and survival. Notably, our results highlight that AST factor expression undergoes dynamic changes during metastasis, which can be reversed in circulating tumor cells. Our findings revealed that AST contributes to the increased metastatic potential and invasiveness of melanoma cells and underscores its role independent of the epithelial-to-mesenchymal-like transition pathways. Based on the results, we highlight the potential of targeting AST mechanisms to develop new therapeutic strategies against metastasis.