Metastatic breast cancer is one of the leading causes of death in women in the United States. Tumor metastasis generally marks the point after which medical intervention can do very little to keep the patient alive. We are interested in exploring metastasis through an integrated approach that studies cancer cells in the context of their surrounding stroma. Host stromal cells such as bone-marrow derived Mesenchymal Stem Cells (MSC) have been shown in previous studies to increase the metastasis of human MDA-MB-231 (MDA) to vital secondary sites such as the lungs. We showed that one of the markers of MDA-MSC interaction is the up-regulation of Interferon (IFN) response genes and that RNAi knock down of these genes inhibits the migration of MDA cells. Using a pharmacological approach, we found that Tubacin, an HDAC-6 specific small molecule inhibitor, down-regulates IFN response genes and inhibits metastatic behavior of MDA cells in vitro. Our study surveys interferon signaling in the tumor microenvironment and shines a spotlight on small molecule inhibitors of IFN activation pathway as potential anti-metastatic drugs.
PROJECT: Targeting Type-1 Interferon Associated Genes in Microenvironment-Induced Breast Cancer Metastasis
The Broad is a place like no other where your scientific aspirations are nurtured and your contribution, both as an individual and as part of a team, is valued. SRPG at the Broad Institute provided me with the opportunity to draw inspiration from the ‘giants of science’ who are refreshingly down-to-earth and eager to offer their invaluable guidance not just for the summer but for the rest of our careers. I learned that science is not only about doing research but moving the field forward by mentoring future scientists, growing intellectually by challenging one another, and working in collaboration to paint the big picture that meets society’s expectations by solving present-day problems.