Discovery of role of Monad in suppressing spread of breast cancer

Jul 4, 2013

Under the leadership of SAEKI Makio , Lecturer, Department of Pharmacology, Graduate School of Dentistry, Osaka University, a group of researchers discovered that the gene Monad (that they discovered in 2006) functions in suppressing the invasiveness, the metastasis, of breast cancer tumors.
These findings are the result of joint research by Department of Breast and Endocrine Surgery, Graduate School of Medicine, Osaka University and the University of Toronto.
Following the insertion of Monad into breast cancer cells with strong invasiveness, the cells became noninvasive. It was also found that Monad expression decreased in patients whose breast cancer had spread to their lymph nodes. Thus, if therapeutic compounds that enhance Monad expression can be produced, such treatment would likely suppress breast cancer invasion and metastasis. This discovery is promising in leading to the development of new therapeutic treatments for breast cancer.

Abstract

Increased stabilization of mRNA coding for key cancer genes can contribute to invasiveness. This is achieved by down-regulation of exosome cofactors, which bind to 3'-UTR in cancer-related genes. Here, we identified amphiregulin, an EGFR ligand, as a target of WD repeat protein Monad, a component of R2TP/prefoldin-like complex, in MDA-MB-231 breast cancer cells. Monad specifically interacted with both the 3'-UTR of amphiregulin mRNA and the RNA degrading exosome, and enhanced decay of amphiregulin transcripts. Knockdown of Monad increased invasion and this effect was abolished with anti-amphiregulin neutralizing antibody. These results suggest that Monad could prevent amphiregulin-mediated invasion by degrading amphiregulin mRNA.

To learn more about this research, please read the full research report entitled " Exosome-Bound WD Repeat Protein Monad Inhibits Breast Cancer Cell Invasion by Degrading Amphiregulin mRNA " at this page of the PLOS One website.

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