Guan and his colleagues used a cultured cell line to study cancer, which are mouse cells grown in the lab for research purposes. The researchers used these cells to create a model system for cancer cells, which means its basic pathway exists in real-world systems, while the actual proteins that act on the system may vary.
In the model system, the researchers discovered critical differences between cancer cells and normal cells regarding a mechanism called endocytosis -- which cells employ to let materials enter through the cell membrane.
The researchers used a protein called v-Src derived from an oncogenic virus, which has the ability to transform a normal cell into one with many features resembling those found in cancer cells. While this virus has not been found in humans, it does lead to tumor growth in chickens and created cancerous cells in the cultured system. In the study, the researchers found that v-Src attaches to an enzyme, called focal adhesion kinase, inside the cell. This association jump-starts a series of cascading interactions between proteins in the cell that ultimately block some cell-surface proteins from entering through the cell's membrane.
One of the proteins not allowed entry is called MT1-MMP. As this material accumulates on the cell surface, it degrades the connective tissue that holds the cancerous cell in place. The build-up of MT1-MMP also activates an enzyme called MMP2, which further degrades the connective tissue. In this way, the cancer cell loses its moorings and can float off to spread around the body. While no one has found v-Src in human cancer patients, a number of other cancers have been linked to viruses, including the herpes virus and its association with cervical cancer.
"Critics of this work will ask why v-Src has not been found in human cancer," said Guan. "But there are many examples of studies and ideas that come out of work like this that stimulate related research with clinical impacts.
"We looked at a relatively late stage of cancer and its spread within the body," Guan added. "The spreading part is less well understood, and it's the spreading that is killing people."
The National Institutes of Health supported this research. Xiaoyang Wu, a graduate student in Guan's laboratory, co-authored the study.