Melanopsin (OPN4) is a light-sensitive protein found in skin and retinal cells. A new study from the University of São Paulo (USP) in Brazil suggests that OPN4 may also be involved in the development and progression of melanoma, the most aggressive type of skin cancer.
In experiments with animals and genetically modified cells at the Institute for Biological Sciences’ Laboratory for Comparative Pigmentation Physiology (IB-USP), researchers have shown that the disease progresses more slowly when this protein is not functioning. The findings are presented in an article published in Communication biology Springer Nature magazine.
Although other groups have already shown that opsins are involved in cancer development, this is the first such discovery 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 for the study was a study by the same group using models of melanocytes (melanin-producing skin cells) to show that melanopsin is expressed in these cells and is involved in processes such as pigmentation, the setting of biological clocks, and even cell death due to ultraviolet A radiation. .
The latest study used a DNA editing technique known as CRISPR to resequence the Opn4 gene and create a stable model of melanoma cells with a non-functional version of the protein.
When we created knockout cells [without a functional OPN4 gene], we realized that they had a completely different phenotype: they grew less and showed a reduced proliferative capacity. We wondered why and set out to find out if melanopsin plays a role in melanoma progression or carcinogenesis.”
Leonardo Vinicius Monteiro de Assis, first author of the study and researcher at the University of Lübeck
Assis collaborated on the study with José Talles Lacerda, co-author of the paper.
The theory was confirmed first in experiments conducted in vitro and then in animals. Tumor cells containing a non-functional version of OPN4 grew smaller and slower than wild-type cells (without OPN4 modification). The discovery was later confirmed using proteomics and data from public databases.
“Overall, we have shown that when OPN4 is removed in melanoma, cell growth is reduced. This is mainly 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 by GTPases, proteins that resemble tiny motors that play a role in cell cycle progression and are significantly downregulated in these tumors,” Assis said.
The study also showed that MITF (microphthalmos-associated transcription factor), a very important transcription factor in melanoma, is also much less expressed in cells with a non-functional version of melanopsin.
According to Assis, all these data together suggest for the first time that melanopsin acts as an oncogene in melanoma, that is, that it is associated with the development and growth of this type of cancer. Until now, melanopsin has never been associated with the development of tumors. More experiments on melanoma cell lines and other approaches are needed to arrive at definitive confirmation of this role.
The Laboratory for Comparative Physiology of Pigmentation, led by physiologist Ana Maria de Lauro Castrucci, is one of the few research groups worldwide to demonstrate (in 2018) that melanopsin also detects temperature, acting independently as a thermosensor and photosensor. With the new information, he added another important aspect, showing that the molecule could be a promising therapeutic tool in the future.
“Melanopsin can be used to treat melanoma, and this opens up new possibilities for studying its role in other diseases, such as liver disease, where opsins are also present,” said Assis.
The Castrucci lab is currently investigating the systemic role of melanopsin in organs it does not normally affect, such as adipose tissue, the liver, and the heart, among others.
Source:
Sao Paulo State Research Support Foundation
Link to the journal:
Assisi, LVM, and others. (2022) Melanopsin (Opn4) is a skin melanoma oncogene. Communication biology. doi.org/10.1038/s42003-022-03425-6.