Insights into melanoma initiation offer new therapeutic opportunities
Researchers from VIB and KU Leuven uncovered a key vulnerability of melanoma. While studying the role of the melanoma-specific long non-coding RNA SAMMSON in tumor initiation, the researchers found that it boosts protein synthesis in different cellular compartments. Normal 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, by altering the protein production in two different compartments, SAMMSON prevents the normal cells from recognizing the oncogenic threat resulting in unrestrained cell growth. 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.
SAMMSON has a role in melanoma initiation
Recent insights indicated that a large share of the human genome doesn't contribute to protein coding, but is nevertheless transcribed and thus produces non-coding RNAs that have a huge influence on essential biological processes and diseases.
"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" says Roberto Vendramin (VIB-KU Leuven), the main author of the paper. "We now know that SAMMSON is a melanoma-specific oncogene and thus its expression is an essential step in melanoma initiation", confirms Prof. Marine (VIB-KU Leuven).
The process of protein production occurs in two cellular compartments: the cytosol and the mitochondria (also known as the powerhouses of the cell). Synchronization of mitochondrial and cytoplasmic translation rates is critical for cellular fitness, and cancer cells are especially vulnerable to translational uncoupling. "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." says Prof. Leucci (KU Leuven).
Next steps: impairment of mitochondrial translation as a melanoma vulnerability
This work established the importance of coordinated translation regulation for cancer progression and the essential role of SAMMSON in this process in melanoma. Prof. Leucci: "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." VIB and collaborators are actively pursuing translation of the findings reported in Vendramin et al. and the previous paper for the benefit of patients.
Vendramin et al., SAMMSON fosters cancer cell fitness by concertedly enhancing mitochondrial and cytosolic translation in Nature Structural and Molecular Biology.
The study is supported by the King Baudouin Foundation (Fund Emile Carpentier – Fund Andre? Vander Stricht – Fund Van Damme 2017-J1810830-207301) and led by professor Eleonora Leucci (KU Leuven) and professor Chris Marine (VIB-KU Leuven). Roberto Vendramin is supported by an FWO fellowship.
Questions from patients
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