Melanopsin (OPN4) is a light-sensitive 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 in the Comparative Physiology of Pigmentation Laboratory at the Institute of Biosciences (IB-USP), the researchers showed that the disease progresses more slowly when this protein is not functional. The findings are reported in an article published in Communication biology a Springer Nature magazine.
Although other groups had already shown that opsins are involved in cancer, this is the first finding for melanoma, which is responsible 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 for the study was a study 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 alter the sequence of the Opn4 gene and create a stable melanoma cell model containing a non-functional version of the protein.
When we made the knockout cells [without a functional OPN4 gene], we realized that they had a very different phenotype: they grew less and showed a reduced proliferative capacity. We wondered why and decided to find out whether melanopsin played a role in melanoma progression or carcinogenesis.”
Leonardo Vinícius Monteiro de Assis, lead author and researcher of the study, University of Lübeck
Assis collaborated on the study with José Talles Lacerda, the second author of the article.
The theory was confirmed first in experiments performed in vitro and then in animals. Tumor cells containing the non-functional version of OPN4 grew less and more slowly than wild-type cells (without modification of OPN4). The discovery was later confirmed using proteomics and data from public databases.
“Basically, we’ve shown that cell growth in melanoma decreases when you remove OPN4. This is actually due to two processes that aren’t necessarily related, but could be: increased immune system activation, although we don’t yet know why; and a very significant reduction in signaling by GTPases, proteins that resemble 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, that is, it is associated with the development and growth of this type of cancer. Until now, melanopsin had never been associated with tumorigenesis. More experiments with melanoma cell lines and other approaches are needed to definitively confirm this role.
The Comparative Physiology of Pigmentation Laboratory, led by physiologist Ana Maria de Lauro Castrucci, is one of the few research groups worldwide that (in 2018) has shown that melanopsin also detects temperature and acts independently as a thermosensor and a photosensor. With the new information, it has now added another important aspect by showing that the molecule could become a promising therapeutic tool in the future.
“Melanopsin could be investigated 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 that it is classically not known to affect, such as adipose tissue, the liver and heart, among others.