Prostate cancer is the most common form of cancer in men. The manifestation of distant metastasis is the major cause of cancer-related deaths. The metastatic dissemination is an inefficient, complex and dynamic process, involving tumour cells detaching from the primary tumour site, entering the bloodstream, extravasation at distant locations and establishing secondary tumours. The reciprocal regulation of miRNA and their targets has been established as crucial regulators of the balance between epithelial and mesenchymal differentiation states, as well as cancer stem cell regulation.
We focus on the miRNA regulation of the transient processes leading to metastases as the reversibility of this type of regulation present a possible interference option. Different miRNAs have evolved to coordinate the regulation of hundreds of genes involved in coordinated cellular functions. When these functions are disrupted in e.g. cancer progression, they provide a strategy to target systems rather than one-gene-at-a-time in a fine-tuned manner. We perform molecular and functional characterisation of primary tumour cells, the heterogeneous population of circulating tumour cells and exosomes, and confirm our findings in clinical cohorts. To identify the molecular characteristics defining the different steps of tumour progression and metastatic spread, will increase the understanding of cancer metastasis and can also lead to the development of improved patient-oriented strategies for combating cancer, and provide novel means to monitor the disease progression and treatment response.