The findings could point to a new approach to cancer treatment.
The study was published this week as the cover article of the journal Science Signaling.
The focus of the study was angiomotin, a protein that coordinates cell migration, especially during the start of new blood vessel growth and proliferation of other cell types.
“We were the first to describe angiomotin’s involvement in cancer,” said Joseph Kissil, a TSRI associate professor who led the studies. “ And while some following studies found it to be inhibiting, we wanted to clarify its role by using both cell studies and animal models. As a result, we have now found that it is not an inhibitor at all, but instead is required for Yap to produce new tumor growth.”
Yap (Yes-associated-Protein) is a potent oncogene that is over-expressed in several types of tumors.
In addition to identifying angiomotin’s critical role in tumor formation, Kissil and his colleagues found the protein is active within the cell nucleus. Earlier cell studies focused on the function of the protein at the cell membrane.
“This pathway, which was discovered less than a decade ago, appears to regulate processes that are closely linked to cancer,” Kissil said. “The more we study it, the more we see its involvement.”
The first authors of the study, “The p130 Isoform of Angiomotin Is Required for Yap-Mediated Hepatic Epithelial Cell Proliferation and Tumorigenesis,” are Chunling Yi of Georgetown University Medical Center and Zhewei Shen of the University of Pennsylvania. Other authors include Anat Stemmer-Rachamimov of Massachusetts General Hospital; Noor Dawany, Louise C. Showe and Qin Liu of The Wistar Institute; Scott Troutman of TSRI; Akihiko Shimono of TransGenic, Inc.; Marius Sudol of Geisinger Clinic; Lars Holmgren of Karolinska Institutet, Stockholm; and Ben Z. Stanger of the University of Pennsylvania. For more information, see http://stke.sciencemag.org/cgi/content/abstract/sigtrans;6/291/ra77
This study was supported by the National Institutes of Health (grant numbers DK083355 and DK083111; CA142295 and NS077952; and CA0180815 and CA132098), the Commonwealth of PA (66651-01), the PA Breast Cancer Coalition (60707 and 920093), the Abramson Family Cancer Research Institute, the Geisinger Clinic, the Pew Charitable Trusts, the Children’s Tumor Foundation, the Georgetown Lombardi Cancer Center, a Cell and Molecular Biology training grant (GM 07229-35) and a Cancer Center Support Grant (CA051008).
About The Scripps Research Institute
The Scripps Research Institute (TSRI) is one of the world’s largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including three Nobel laureates—work toward their next discoveries. The institute’s graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
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