Abstract

Cancer–Host Crosstalk Through Exosomal miRNA

Shizhen Emily Wang, Associate Professor, Department of Pathology, University of California, San Diego

Extracellular microRNAs (miRNAs) that can be detected in the circulation are novel mediators of intercellular communication and are considered emerging biomarkers for human diseases. Using cell-secreted extracellular vesicles (e.g., exosomes) as vehicles, miRNAs secreted by cancer cells can travel to and enter various types of niche cells in primary and pre-metastatic tumor microenvironments. Upon entering niche cells, miRNAs regulate gene expression to prepare the niche for cancer progression. Our lab focuses on defining the roles of breast cancer secreted miRNAs in adapting local and distal niche cells and tissues in cancer progression and metastasis. Through de novo sequencing and PCR of circulating small RNAs in the sera of breast cancer patients we identified circulating miRNAs as biomarkers for cancer progression to metastatic disease. Subsequent mechanistic studies revealed important functions of breast cancer secreted miRNAs in various aspects of cellular behaviors. Our findings reveal (1) vascular leakiness and enhanced metastasis caused by cancer-secreted miR-105, which downregulates endothelial tight junctions; (2) miR-105-induced metabolic plasticity in cancer-associated fibroblasts to convert cancer-produced metabolic wastes (e.g., lactate and ammonia) into energy-rich metabolites to re-enter cancer bioenergetics; (3) suppressed glucose utilization by lung fibroblasts and astrocytes in favor of glucose uptake by metastasized cancer cells mediated by cancer-secreted miR-122.