New therapeutic opportunities discovered from melanoma initiation

A vital vulnerability of melanoma initiation has been uncovered by researchers, finding that specific RNA boosts protein synthesis in different cellular compartments.

Researchers from VIB-KU Leuven Center for Brain & Disease Research, Belgium, uncovered a key vulnerability of melanoma. Studying the role of the melanoma-specific long non-coding RNA SAMMSON in melanoma initiation, the researchers found that it boosts protein synthesis in different cellular compartments. Regular cells are alerted by modification in protein synthesis and react to this threat, but only if this process is altered in one compartment at the time.

However, SAMMSON stops the normal cells from identifying the oncogenic threat resulting in unrestrained cell growth, by altering the protein production in two different compartments. The scientists suggest that any substance that destroys the equilibrium carefully created by SAMMSON is expected to deliver highly effective anti-melanoma responses.

The study is published in the scientific journal Nature Structural and Molecular Biology.

Melanoma initiation and the role SAMMSON has

Latest research indicates that a large share of the human genome doesn’t contribute to protein coding but is nevertheless transcribed, therefore producing non-coding RNAs that have a huge influence on essential biological processes and diseases.

Roberto Vendramin, from VIB-KU Leuven and the main author of the paper explains: “We have already demonstrated that SAMMSON appears early in the process of melanoma genesis and we were wondering whether this is an important event in cancer initiation.”

“We now know that SAMMSON is a melanoma-specific oncogene and thus its expression is an essential step in melanoma initiation.” Confirms Proffessor Marine, VIB-KU Leuven.

The cytosol and the mitochondria are the two cellular compartments where the process of protein production occurs. Synchronization of mitochondrial and cytoplasmic translation rates is essential for cellular fitness, and cancer cells are especially vulnerable to translational uncoupling.

Colleague Professor Leucci further explains: “Our work now proves that SAMMSON, which is aberrantly expressed in melanoma, has an essential role in this process by concertedly enhancing protein synthesis in the cytosol and mitochondria.”

“SAMMSON behaves as a selfish molecule that tries to perpetuate its own expression by increasing proliferation of malignant cells through increased translation.”

Next steps: from melanoma initiation to exploring other possibilities

This research has recognised the importance of coordinated translation regulation for cancer progression and the essential role of SAMMSON in this process in melanoma.

Leucci concludes: “Considering the fundamental nature of this phenomenon we will explore the possibility that other long non-coding RNAs can exert the same function in melanoma and other cancers.”

“Perhaps more importantly, the results of this collaborative effort can serve as a solid foundation towards new skin cancer treatments that interfere with the translational activity in the mitochondria.”