Study Reveals Role of Genetic Switch in Pigmentation and Melanoma

Jill Murphy, Associate Editor

Melanoma forms when pigment-producing cells called melanocytes mutate and multiply uncontrollably.

A recent study by The Salk Institute reveals new insights about a protein called CRTC3, a genetic switch that could potentially be targeted to develop new treatments for melanoma by keeping the switch turned off.

“We’ve been able to correlate the activity of this genetic switch to melanin production and cancer,” said Salk study corresponding author Marc Montminy, a professor in the Clayton Foundation Laboratories for Peptide Biology, in a press release.

Melanoma forms when pigment-producing cells called melanocytes mutate and multiply uncontrollably. The melanocyte mutations lead to proteins such as CRTC3 to cause cells to begin producing an abnormal amount of pigment or to migrate and be more invasive, according to the study authors.

The researchers said the CRTC family of proteins (CRTC1, CRTC2, and CRTC3) is known to be involved in pigmentation and melanoma; however, they noted that it has been difficult to procure specific information about the individual proteins.

“This is a really interesting situation where different behaviors of these proteins, or genetic switches, can actually give us specificity when we start thinking about therapies down the road,” said first author Jelena Ostojić, a former Salk staff scientist and now a principal scientist at DermTech, in the press release.

The research team found that when CRTC3 was removed in mice models, it caused a color change in the animal’s coat color, which indicates that the protein is necessary to produce melanin. The study authors additionally found that when CRTC3 was missing in melanoma cells, the cells migrated and became less aggressive, which indicates that inhibiting the protein could benefit treatment of the disease.

The researchers were able to characterize for the first time the connection between 2 cellular signaling systems that join on the CRTC3 protein in melanocytes, according to the study. These 2 systems guide the cell to either multiply or to produce melanin.

Montminy compared the process to a relay race, in which the chemical message is passes among proteins until it reaches the CRTC3 switch, either turning it on or off.

“The fact that CRTC3 was an integration site for two signaling pathways—the relay race—was most surprising,” Montminy said in the press release. “CRTC3 makes a point of contact between them that increases specificity of the signal.”

In future studies, the researchers will further evaluate the mechanism of how CTRC3 impacts the balance of melanocyte differentiation to improve the understanding of its role in cancer development.

REFERENCE

Salk scientists reveal role of genetic switch in pigmentation and melanoma. Salk. Published May 18, 2021. Accessed May 19, 2021. https://www.salk.edu/news-release/salk-scientists-reveal-role-of-genetic-switch-in-pigmentation-and-melanoma/