Functional genomic screens for novel metastasis suppressor genes in breast and prostate cancer models

Abstract

Metastasis is the predominant cause of mortality in many cancers, including prostate and breast cancers. With a substantial number of men and women being diagnosed with these cancers each year in the United States, there is a need for effective methods to rapidly identify key regulators of the metastatic cascade that can subsequently be employed in diagnostic, prognostic, and therapeutic applications. This has become increasingly important as we come to understand that many metastatic events occur earlier in disease progression than originally thought. Functional genomic screens have arisen as an effective means to rapidly screen for critical genes controlling a specified biology. Loss of function screens, such as RNAi libraries, are particularly useful for the identification of suppressor genes. We utilized genome-wide RNAi screens to identify negative regulators of metastasis, defined as metastasis suppressor genes, with in vivo and in vitro breast and prostate cancer models. We performed multiple screens assessing the individual contributions of genes in Matrigel invasion (T-47D), initial colonization of lungs by prostate cancer cells (LNCaP) in a mouse model, and complete metastasis from orthotopic tumor to distant metastases in vivo (LNCaP).