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Melanopsin (OPN4) is a light-sensing protein found in skin and retinal cells. A new study conducted at the University of São Paulo (USP) in Brazil suggests that OPN4 may also participate in the development and progression of melanoma, the most aggressive type of skin cancer.In experiments with animals and genetically modified cells at the Comparative Physiology of Pigmentation Laboratory belonging to the Institute of Biosciences (IB-USP), the researchers showed that the disease develops more slowly when this protein is not functional. The results are reported in an article published in Communication biology a Springer Nature journal.Although other groups had already shown that opsins are involved in cancer, this is the first such finding for melanoma, which accounts for 5% of malignant skin tumors and 80% of all cancer deaths. The study was supported by FAPESP (projects 17/24615-5, 17/26651-9, 18/14728-0 and 19/19005-9.The basis of the study was a study carried out by the same group using models of melanocytes (melanin-producing skin cells) to show that melanopsin was expressed in these cells and participated in processes such as pigmentation, biological clock adjustment and even cell death due to ultraviolet A- radiation.The latest study used the DNA editing technique known as CRISPR to change the sequence of the gene Opn4 and create a stable melanoma cell model with a non-functional version of the protein.When we created the knockout cells [without a functional OPN4 gene], we realized that they had a very different phenotype: they grew less and showed reduced dispersal ability. We wondered why and decided to find out if melanopsin played a role in melanoma progression or carcinogenesis.”Assis collaborated on the study with José Thales Lacerda, the paper’s second author.The theory was first confirmed in experiments carried out in vitro and then in animals. Tumor cells containing the non-functional version of OPN4 grew smaller and slower than wild-type cells (without modification of OPN4). The discovery was later confirmed using proteomics and data from public databases.“In sum, we showed that cell growth decreases in melanoma when you remove OPN4. This is basically due to two processes that are not necessarily related, but may be: increased activation of the immune system, although we do not yet know why; and a very significant reduction in signaling GTPases, proteins that look like small motors that play a role in cell cycle progression and are greatly reduced in these tumors,” Assis said.The study also revealed that MITF (microphthalmia-associated transcription factor), a very important transcription factor in melanoma, is also much less expressed in cells with the non-functional version of melanopsin.According to Assis, all these findings together suggest for the first time that melanopsin acts as an oncogene in melanoma, i.e. that it is associated with the development and growth of this type of cancer. Until now, melanopsin had never been linked to the development of tumors. More experiments on melanoma cell lines and other approaches are still needed to arrive at a definitive confirmation of this role.The Comparative Physiology of Pigmentation Laboratory, led by physiologist Ana Maria de Lauro Castrucci, is one of only a few research groups worldwide to have demonstrated (in 2018) that melanopsin also detects temperature and functions independently as a thermosensor and a photosensor. With the new information, it has now added another important aspect by showing that the molecule may become a promising therapeutic tool in the future.“Melanopsin could be explored for the treatment of melanoma, and this opens a new avenue for research into its role in other diseases, such as those of the liver, where opsins are also present,” Assis said.Castrucci’s lab is currently investigating the systemic role of melanopsin in organs it is not classically known to affect, such as adipose tissue, the liver, and the heart, among others.