Molecule may hold key to melanoma progression

The search for new pathways to treat melanoma has unearthed a molecular target that may play an important activation role in tumour growth, according to University of Newcastle researchers.

Where many cancer researchers look for mutated genes that are over-expressed, in this case the team discovered that a molecule called PIB5PA is down-regulated in melanoma.

“The molecule should be expressed, it should be keeping the cell normal, but it is lost,” research leader Professor Xu Dong Zhang said. “This loss activates a specific pathway called Akt, which occurs in up to 70% of melanomas.

“The pathway plays an important role in the development of melanomas and in their progression and resistance to treatment.”

In results published in the online journal Nature Communications, the team found it could inhibit the growth of melanoma cells, and even shrink them, by restoring the expression of PIB5PA and inhibiting activation of Akt.

“We need to further explore the mechanisms that suppress this molecule but it provides a potential new treatment approach, where currently there are no effective therapies for this type of melanoma,” Professor Zhang said.

The paper resulted from extensive local, national and international collaboration over three years, with 21 authors from 10 institutes in Australia and China. The team from University of Newcastle included molecular biologist Dr Rick Thorne and co-authors Lei Jin and Chen Chen Jiang.

“Our previous research had hinted that PIB5PA was interesting in the Akt pathway and we pursued this in the context of melanoma,” Dr Thorne said. “PIB5PA turned out to be a key regulatory mechanism that is deregulated in melanoma.

“There are tens of thousands of genes in every cell so discovering the important ones is an art. It takes a lot of work and a lot of faith but Xu Dong has a knack for picking the right molecules.”

The team is now exploring targeted approaches to blocking the Akt pathway while examining whether PIB5PA can serve as a biomarker for likely progression of some melanomas.