Researchers take a one health approach, shedding light on the control of cancer across plants, animals, and humans
Arabidopsis, or mouse-ear cress
UMD researchers have identified genetic mechanisms to control cancer-like growths in the plant Arabidopsis, commonly known as mouse-ear cress. The cancer-like tumors as a result of a mutated gene in the plant cause the formation of abnormal flowers and sterility, and the cell cycle complexes disrupted in the mutant plant work similarly in animal and human cells to regulate cell division and organ growth. Using the latest CRISPR gene editing technology, researchers are now able to correct the cancer-like behavior in the plant and have elucidated the underlying mechanisms relevant plants, animals, and humans. With this ability and a clearer understanding of the mechanisms that contribute to uncontrolled cell growth, a path can be laid to the control of plant, animal, and human cancers connected to these genes.
Mouse-ear cress is a small flowering plant closely related to mustard and cabbage plants, and it is often used as a model system given its genetic similarities across plants, animals, and humans and how easy it is to propagate. Dr. Zhongchi Liu, Affiliate Professor with the Department of Plant Science and Landscape Architecture and Professor in the Department of Cell Biology and Molecular Genetics, works with mouse-ear cress often in her research. She named the TSO1 gene she discovered in mouse-ear cress after the Chinese word for “ugly” because of the large cancer-like blobs found in the mutated plant where flowers should be.
“Cancer is caused by a series of genetic mutations that result in uncontrolled cell proliferation and failure of differentiation” explains Liu. “There are so many types of cancer because there are so many genes and combinations of mutations that can lead to this uncontrolled or abnormal growth in any tissue in the body of any plant, animal, or human. Any insight into a series of genes that contribute to uncontrolled cell proliferation and cancer-like growths can provide connections to parallel genes in animals and humans. That makes this work very exciting.”
The TSO1 gene (aka the ugly gene) is a regulatory gene whose gene product is a member of a cell cycle complex known as the DREAM complex. This complex is conserved and similar to regulatory complexes in animals and humans known to balance cell proliferation and differentiation, determining what cell should be what cell type and how much of it is needed. When these things get out of control, tumors and cancers form. “There are always multiple genes at work that control and produce one phenotype or physical trait, whether that trait is a beautiful and healthy flower or a cancer-like ‘ugly’ blob,” says Liu.
In this case, in addition to identifying the ugly gene, Liu and her team recently identified the MYB3R1 gene as another component in the DREAM complex; this second gene works together with TSO1 to control plant cell growth. “Excitingly, the MYB3R1 gene we found in the plant is highly similar in protein sequence to the MYB previously found in animals and humans,” says Liu. “We found that inactivating the MYB3R1 gene through gene editing and mutation completely reverses the blob ‘ugly’ phenotype in the plant, so normal flowers are produced and cancer-like tumors are no longer present. The genetic interactions between the ugly gene and its partner MYB gene and their functional roles in regulating healthy tissue and organ growth hadn’t been observed before, and they give us useful information about how cell growth and differentiation in tissues and across the whole body is regulated potentially not just in plants, but in animals and humans.”
This work is published in The Proceedings of the National Academies of Science here.
