Protein That Drives Melanoma Development Identified

Findings improve the ability of providers to monitor the development of melanoma.

A research team has discovered a protein that drives the development of melanoma, which could help identify aggressive tumors.

The study, published in Cell Reports, identified a malicious form of the protein ATF2. Researchers examined the oncogenic potential of a deadly form of ATF2 in mice with mutations in BRAF.

“We found that an inactive version of a protein called activating transcription factor 2 (ATF2) elicits a tumor-promoting effect in a way not seen before,” said senior study author Ze'ev Ronai, PhD. “We have known for years that the active version of ATF2 promotes melanoma, but this result was a surprise because we thought ATF2 transcriptional activity was essential to activate cancer-related genes.”

The results of the study revealed the inactive ATF2 caused a formation of pigmented lesions in the mice that later turned into melanoma tumors.

“What makes this discovery relevant to human melanoma is that we identified a structurally similar form of inactive ATF2 in human melanoma samples that has the same effects on cancer cells,” Ronai said. “Inactive ATF2 could be an indicator of tumor aggressiveness in patients with BRAF mutations, and maybe other types of cancer as well.”

Models with more complex genetic changes, such as the inactivation of PTEN and p16 plus BRAF mutations, resulted in rapid tumorigenesis. In the current study, the inactive ATF2 caused the BRAF mutant mice to develop melanoma at a slower pace, similarly to that seen in patients.

“This improves our ability to monitor the development of melanoma and efficacy of possible interventions,” Ronai said.

Researchers are now exploring why inactive ATF2 causes this.

“We're now investigating why inactive ATF2 so potently promotes BRAF-mutant melanoma, and looking for other types of cancer where it acts the same way,” Ronai said. “Our findings may guide precision therapies for tumors with mutant ATF2.”