The role and signaling pathway of microRNA-30a in breast cancer progression

Breast cancer is the most frequent cancer among women in the United States with over 230,000 new cases and 40,000 deaths every year. Metastasis and therapy resistance are the two major fatal problems. The big question is, what are the cellular and molecular mechanisms linking these two phenotypes? We propose that breast tumor initiating cells with stem cell properties are able to mediate both metastasis and therapy resistance. We hypothesize that one of the underlying molecular mechanisms linking metastasis and therapy resistance is through microRNA regulation. We have identified miR-30a as a prognostic marker and functional regulator of both breast cancer metastasis and chemoresistance. This project will further examine its regulatory role in patient-derive breast tumor xenografts in vivo and dissect the signaling pathway through the downstream target genes, transcription factors, and a cytokine IL-11. Notably, our studies have identified IL-11 as a promising novel therapeutic target. In this project, we are developing an antibody-based innovative strategy to inhibit metastasis and sensitize chemotherapy in patient-derived human-in-mouse breast tumor models. We will also utilize the cutting-edge imaging technology to facilitate the understanding of basic biology and applications of our discoveries into clinical settings.