Could lead to new approaches for targeting cancer metastasis
A University of Nebraska Medical Center research team has used genetically engineered cells to show the role of a new molecular pathway in controlling a key cellular protein needed for normal cell movement and cancer cell metastasis.
The discovery could translate into novel strategies to stop the spread of cancer cells from their primary site into distant sites, the deadly transition known as metastasis that is ultimately responsible for essentially all cancer-related deaths.
The research was reported in the Sept. 14 issue of the Proceedings of the National Academy of Sciences, a leading science journal.
The study was carried out by a UNMC Eppley Cancer Center team headed by Hamid Band, M.D., Ph.D., professor and associate director of translational research, and Chun Tu, M.D., Instructor, in collaboration with Vimla Band, Ph.D., professor and chairwoman, department of genetics, cell biology and anatomy, College of Medicine, and Kay-Uwe Wagner, Ph.D., professor at the Eppley Institute.
When the gene coding for the protein TSG101 (Tumor Suppressor Gene 101) was deleted in cells, the cell movement-promoting protein c-Src could not reach its site of action efficiently.
The c-Src protein, the first oncogene identified more than 30 years ago, is found at higher levels in a number of human cancers such as breast, lung and colon cancer.
The study provides key new insights into how the active form of c-Src finds its way from an intracellular location where it cannot participate in promoting cell migration to where its presence is essential for a cell to move.
Identification of molecular pathways that an oncogene such as c-Src must travel to reach its site of action has obvious implications for designing inhibitors to halt cancer cells from moving, Dr. Band said.
He said c-Src is a kinase, an enzyme that exerts regulatory effects on growth and malignant transformation by cancer-inducing proteins. Some kinase inhibitors targeting c-Src already have been developed and are being used in cancer treatment.
The present findings could provide a basis for a newer generation of therapeutic agents to target this pathway, Dr. Band said, and facilitate discovery of other genes involved in the new pathway while helping investigators better understand how c-Src contributes to cancer.
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Photo of Dr. Hamid Band (click on this link)
