Proteoglycans Determine the Dynamic Landscape of EMT and Cancer Cell Stemness

SIMPLE SUMMARY: Proteoglycans are important structural and functional components of extracellular matrices that govern phenotype and functions of resident cells. They are often deregulated in cancer cells and their stroma, providing a favorable microenvironment for cancer cell growth and spread. Proteoglycans, by influencing cell–cell and cell–matrix interactions and oncogenic signaling, affect cancer cell phenotype and properties. In this article, we discussed the implication of proteoglycans with cancer cell stemness and epithelial-to-mesenchymal transition. ABSTRACT: Proteoglycans (PGs) are pivotal components of extracellular matrices, involved in a variety of processes such as migration, invasion, morphogenesis, differentiation, drug resistance, and epithelial-to-mesenchymal transition (EMT). Cellular plasticity is a crucial intermediate phenotypic state acquired by cancer cells, which can modulate EMT and the generation of cancer stem cells (CSCs). PGs affect cell plasticity, stemness, and EMT, altering the cellular shape and functions. PGs control these functions, either by direct activation of signaling cascades, acting as co-receptors, or through regulation of the availability of biological compounds such as growth factors and cytokines. Differential expression of microRNAs is also associated with the expression of PGs and their interplay is implicated in the fine tuning of cancer cell phenotype and potential. This review summarizes the involvement of PGs in the regulation of EMT and stemness of cancer cells and highlights the molecular mechanisms.