Role of miRNAs in cell signaling of cancer associated fibroblasts.

The tumor microenvironment (TME) of cancer cells is regarded as a strong determinant for cancer development and acquisition of metastatic potential of cancer cells. Because of its influence on tumorigenesis, the TME increasingly gained attention in research within the last years. Activated fibroblasts, so-called cancer-associated fibroblasts (CAFs), which are the most prominent cell type in the stromal compartment, are responsible for the synthesis, deposition and remodeling of the extracellular matrix in tumor stroma thus creating a favorable microenvironment for cancer cells. Besides, they secrete paracrine factors, such as growth factors, chemokines and exosomes impacting on proliferation, invasion and cell signaling of cancer cells. Molecular mechanisms responsible for activation of fibroblasts and regulation of metastatic microenvironment are complex and not yet fully elucidated. However, mounting evidence suggests that miRNAs play a powerful role in the communication between cancer cells and TME. Via regulation of various signaling pathways, release of cytokines/growth factors or exosomes, miRNAs are able to regulate tumor promoting effects of CAFs. In this review, we describe baseline differences in miRNAs signatures between CAFs and normal fibroblasts and highlight the influence of miRNAs on cell signaling within CAFs.