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Researchers Revealed Genetic Switch in Melanoma

Melanoma is a type of skin cancer that starts in the cells called melanocytes. While melanoma is less prevalent than basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), it is more hazardous since it can spread to other organs more quickly if not treated early. The CRTC family of proteins (CRTC1, CRTC2, and CRTC3) has long been known to play a role in pigmentation and melanoma, but the proteins' exact functions have remained obscure. Researchers at the Salk Institute have discovered new information on the protein CRTC3, which could lead to new melanoma treatments.

The researchers claim to have discovered a "genetic switch" involving CRTC3 that appears to be important in the progression of melanoma. The paper publish under title  “Transcriptional co-activator regulates melanocyte differentiation and oncogenesis by integrating cAMP and MAPK/ERK pathways.” 

 “We've been able to tie the function of this genetic switch to melanin production and cancer,” said accompanying study author Marc Montminy, MD, PhD, a professor at the Clayton Foundation Laboratories for Peptide Biology.

The researchers found that deleting the CRTC3 gene, but not the CRTC1 or CRTC2 genes, had an impact on pigmentation and melanocyte fitness.

“This is a really interesting situation where different behaviors of these proteins, or genetic switches, might actually provide us specificity when we start thinking about therapeutics down the road,” said Jelena Ostojic, a former Salk staff scientist who is now a principle scientist at DermTech.

The researchers also discovered that melanoma cells that lacked the protein moved and penetrated less. For the first time, the researchers identified the link between two cellular communications (signaling) systems in melanocytes that converge on the CRTC3 protein.

These two systems instruct the cell to proliferate or produce melanin.

“It was surprised that CRTC3 was an integration site for two signaling pathways—the relay race,” Montminy added. “CRTC3 creates a point of contact between them, increasing signal specificity.”

To gain a deeper understanding of CTRC3's role in cancer, the researchers plan to investigate the mechanism by which it affects the balance of melanocyte differentiation in the future.

The researchers stated, "Our findings imply that CRTC3 may have therapeutic value in the treatment of pigmentary diseases, cutaneous melanoma, and maybe other illnesses defined by dysregulated cAMP/MAPK crosstalk."

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