MiR-29/Hsp47 axis regulates ECM transcription network in breast cancer - Pilot Project of the COBRE for the Center for Molecular Medicine

Extracellular matrix (ECM), an essential component of tumor microenvironment, provides not only physical scaffolds to maintain structure of tumor tissue but also various biochemical signals to modulate migration, invasion, and colonization of tumor cells. We have discovered an ECM transcription network from more than 700 human breast cancers, indicating that coordinated action of ECM proteins is crucial for breast cancer development and progression. We have identified Hsp47, a molecular chaperone, as a hub of the ECM network, and miR-29 as a potential regulator of that network. In this proposal, we will test the hypothesis that the miR29/Hsp47 axis promotes EMT and breast cancer metastasis by modulating the ECM microenvironment. Using a series of complementary approaches, including 3D culture model, Confocal imaging techniques, and sophisticate animal model, we will define roles of the Hsp47 in promoting breast cancer metastasis and the downstream targets of Hsp47. We anticipate that the proposed study will significantly advance our knowledge about Hsp47 and the ECM network in breast cancer progression and metastasis. Successful completion of this project will result in the identification of Hsp47 and miR-29 as key regulators of the ECM network and cancer progression and potential therapeutic targets for breast cancer.