A team of researchers at the NCI uncovered a novel protein interaction in mice that promotes metastasis in sarcomas.
The scientists focused on post-translational modifications by examining the role of the protein gp78 in cancer. gp78 tags specific proteins with ubiquitin, which can lead to the destruction of the tagged proteins by the proteasome.
By silencing the activity of gp78, the NCI team found that the spread and survival of cancer cells in animal models was greatly reduced. The researchers also discovered that gp78 interacts with another protein called KAI1, which has previously been shown to interfere with metastasis and is categorized as a metastasis suppressor.
Further investigation showed that silencing gp78 in sarcoma cells caused levels of KAI1 to rise, thus decreasing cancer cell survival. Conversely, in sarcoma cells with high levels of gp78, KAI1 was more frequently tagged for destruction.
The scientists found that this silencing of KAI1 in cancer cells encouraged both cancer cell survival and metastasis. Going a step further, the NCI team examined archived sarcoma tumor samples from patients and found that tumors with low levels of gp78 had higher levels of KAI1 and vice versa.
The findings will be published in the December issue of Nature Medicine and is currently available online.