Melanopsin (Opn4) is an oncogene in cutaneous melanoma

Author(s)

Monteiro de Assis, Leonardo Vinicius ; Lacerda, Jose Thalles ; Moraes, Maria Nathalia ; Dominguez-Amorocho, Omar Alberto ; Kinker, Gabriela Sarti ; Mendes, Davi ; Silva, Matheus Molina ; Martins Menck, Carlos Frederico ; Saraiva Camara, Niels Olsen ; de Lauro Castrucci, Ana Maria

• Document type: Journal article
• Source: COMMUNICATIONS BIOLOGY; v. 5, n. 1, p. 15-pg., 2022-05-13.

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. (AU)

• FAPESP's process: 19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg)
• Grantee: Carlos Frederico Martins Menck
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/25129-2 - Comprehensive characterization of T cells in Pancreatic Ductal Adenocarcinomas
• Grantee: Gabriela Sarti Kinker
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/24217-0 - Mechanisms of tumor resistance to cisplatin: DNA lesions processing and circadian cycle effect
• Grantee: Matheus Molina Silva
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 17/26651-9 - Glaucoma as a model of temporal information disruption: impact on the metabolism
• Grantee: Maria Nathália de Carvalho Magalhães Moraes Figueira Borges
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 18/16511-8 - Involvement of the photosensitive and temporal controlling systems in the development, progression, and metastasis of malignant melanoma: an investigation of novel therapeutic targets
• Grantee: Leonardo Vinícius Monteiro de Assis
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/50214-4 - Biological clock setting by light and temperature: phylogenetic aspects
• Grantee: Ana Maria de Lauro Castrucci
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/14728-0 - Melanopsin as the UVA photoreceptor and its relationship with pigmentation, DNA repair, biological clock and components of the HPA axis: a novel pharmacological target?
• Grantee: Ana Maria de Lauro Castrucci
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/24615-5 - Breaking a paradigm? Melanopsin, a canonical photo-pigment, acting as sensor to entrain the clock in light unexposed organs, and its putative interaction with TRP channels: a trans-disciplinary study involving physiological and pathological aspects
• Grantee: Ana Maria de Lauro Castrucci
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/18781-0 - The role of XPG endonuclease in nuclear RNA transcription and in the maintenance of mitochondrial genome
• Grantee: Davi Mendes
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/04524-8 - Integrating proteogenomics approach and system biology to investigate the role of melanopsin and TRP channels in the circadian rhythmicity
• Grantee: José Thalles Jocelino Gomes de Lacerda
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/24337-4 - Clock genes modulation by UVA/blue light stimulation in normal melan-A and transformed B-16 melanocytes
• Grantee: Leonardo Vinícius Monteiro de Assis
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 17/16711-4 - Role of sirtuin 1 in CD4+ T cell activation and differentiation in obese transplanted engrafted animals
• Grantee: Omar Alberto Domínguez Amorocho
• Support Opportunities: Scholarships in Brazil - Doctorate