Under the microscope, they sparkle like emeralds, these molecules that may hold a key to understanding — and stopping — cancerous growth.
The molecules are protein receptors that bind epidermal growth factor (EGF). Overexpression of the EGF receptor has been linked to multiple types of cancer. Drugs that block the receptor have become routine treatment for colorectal, head and neck and lung cancer.
Scientists wanted to know more about the receptor’s role in cancer.
But they couldn’t see exactly where in tissues it was located or how diseases like cancer altered its movement within cells.
That all changed with the development of a genome editing technology called CRISPR/Cas9.
Using this technology, researchers at Vanderbilt University Medical Center targeted a green fluorescent label to the end of the coding region of the mouse receptor. The result was dazzling. In these mice, the endogenous EGF receptors now glowed in embryonic and adult tissues including the eye, brain and liver.
The fluorescent label also revealed how the movement of EGF receptors between different cell types in the small intestine and colon was altered by cancerous and precancerous conditions.
These findings, reported recently in the journal Cell Reports, suggest that this mouse model of glowing receptors will be a valuable tool for studying receptor signaling and trafficking in normal and diseased tissues, said Robert Coffey Jr., M.D., the paper’s senior author and Ingram Professor of Cancer Research.
Coffey, who directs the Epithelial Biology Center, has been studying the role of the EGF receptor in gastrointestinal cancers since he arrived at Vanderbilt in 1986. That’s the year Vanderbilt biochemist Stanley Cohen, Ph.D., won the Nobel Prize in medicine for his discovery of EGF and its receptor.
Coffey said this report, especially the dynamics of EGF receptor expression in liver cells, was inspired by Cohen’s work. It suggests that this mouse model of glowing receptors will be a valuable tool for studying receptor signaling and trafficking in normal and diseased tissues.
First authors of the study were Yu-Ping Yang, Ph.D., research instructor of Medicine, and postdoctoral fellow Haiting Ma, Ph.D. Also contributing to the work were the laboratories of Vanderbilt faculty members Rebecca Ihrie, Ph.D., Sabine Fuhrmann, M.D., and Bruce Carter, Ph.D.
The research was supported in part by National Institutes of Health grants CA046413, CA151566, CA163563, CA174377, CA095193, EY024373, EY008126 and NS096238