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Melanopsin (Opn4) is an oncogene in cutaneous melanoma

2022; Nature Portfolio; Volume: 5; Issue: 1 Linguagem: Inglês

10.1038/s42003-022-03425-6

2399-3642

Leonardo Vinícius Monteiro de Assis, José Thalles Jocelino Gomes de Lacerda, Maria Nathália Moraes, Omar Domínguez-Amorocho, Gabriela Sarti Kinker, Davi Mendes, Matheus Molina Silva, Carlos Frederico Martins Menck, Niels Olsen Saraiva Câmara, Ana Maria de Lauro Castrucci,

Neurobiology and Insect Physiology Research

Abstract The search for new therapeutical targets for cutaneous melanoma and other cancers is an ongoing task. We expanded this knowledge by evaluating whether opsins, light- and thermo-sensing proteins, could display tumor-modulatory effects on melanoma cancer. Using different experimental approaches, we show that melanoma cell proliferation is slower in the absence of Opn4 , compared to Opn4 WT due to an impaired cell cycle progression and reduced melanocyte inducing transcription factor ( Mitf ) expression. In vivo tumor progression of Opn4 KO cells is remarkably reduced due to slower proliferation, and higher immune system response in Opn4 KO tumors. Using pharmacological assays, we demonstrate that guanylyl cyclase activity is impaired in Opn4 KO cells. Evaluation of Tumor Cancer Genome Atlas (TCGA) database confirms our experimental data as reduced MITF and OPN4 expression in human melanoma correlates with slower cell cycle progression and presence of immune cells in the tumor microenvironment (TME). Proteomic analyses of tumor bulk show that the reduced growth of Opn4 KO tumors is associated with reduced Mitf signaling, higher translation of G2/M proteins, and impaired guanylyl cyclase activity. Conversely, in Opn4 WT tumors increased small GTPase and an immune-suppressive TME are found. Such evidence points to OPN4 as an oncogene in melanoma, which could be pharmacologically targeted.