Metastasizing cancers – cancers that spread throughout the body – are often deadly and difficult to treat. Melanoma, the most aggressive form of skin cancer, can metastasize quickly to various organs.
Recent research from UNC Chapel Hill sheds light on why these tumors move so fast.
In a paper published in the June edition of Cancer Cell, Dr. Norman Sharpless, Wenjin Liu and colleagues discovered that inactivating the gene LKB1 leads to the metastasis of melanoma tumors.
The team of researchers studied tumors of human cells, as well as those of mice that were genetically engineered to develop melanoma. In both groups, they found that mutations in LKB1 enabled the melanoma cells to move and invade other tissue types.
“Our new work shows that LKB1 loss conveys a property on melanoma associated with high-grade tumors: the ability to spread to other organs, to metastasize,” Sharpless said in an interview.
“Tumor cells lacking LKB1 did not necessarily divide more than other melanoma cells, but they did grow more aggressively.”
The research may help advance the treatment of melanoma if doctors can identify patients whose cancers are more likely to spread.
“Screening for mutations in LKB1 and other commonly mutated genes will definitely help us select the best-fit treatment and prevent melanoma from further progressing,” Sharpless said.
Additionally, the inactivation of the LKB1 gene drives other cancers and diseases.
Mutations in the gene are linked to metastasis in lung and cervical cancers. The gene is involved also with “cellular energy sensing,” and when mutated can contribute to diabetes and other disorders.
So the benefits of a drug that could re-activate a mutated LKB1 gene would be wide-ranging.
“There is significant pharmaceutical-company interest in finding drugs that activate LKB1, to prevent the development of cancer and also to treat diseases like diabetes,” Sharpless said.
“We think this work will be important for multiple common human diseases.”