A team led by scientists from The Scripps Research Institute (TSRI) have shown that a protein once thought to inhibit the growth of tumours is instead required for initial tumour growth.

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 tumour growth.”

Yap (Yes-associated-Protein) is a potent oncogene that is over-expressed in several types of tumours.

In addition to identifying angiomotin’s critical role in tumour 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 Tumourigenesis,” 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 Tumour Foundation, the Georgetown Lombardi Cancer Center, a Cell and Molecular Biology training grant (GM 07229-35) and a Cancer Center Support Grant (CA051008).

Source: Scripps