Cancer-associated fibroblasts: a multifaceted driver of breast cancer progression

Cancerous tissue is a complex mix of tumor cells, stromal cells and extracellular matrix (ECM), all of which make up a disordered and aggressive niche in comparison with organized and homeostatic normal tissue. It is well accepted that the tumor microenvironment plays an indispensable role in cancer development, and thus can be recognized as an additional cancer hallmark alongside those that are well established. In breast cancer, cancer associated fibroblasts (CAFs) are the predominant cellular components and play a centric role in the tumor microenvironment since they not only promote cancer initiation, growth, invasion, metastasis and therapeutic resistance but are also involved in microenvironmental events including angiogenesis/lymphangiogenesis, ECM remodeling, cancer-associated inflammation and metabolism reprogramming, all of which are known to have pre-malignancy potency. At the molecular level, there is a sophisticated network underlying the interactions between CAFs and epithelial cells as well as other stromal components. Accordingly, targeting CAFs provides a novel strategy in cancer therapy. Herein, we summarize the current understanding of the role of CAFs in breast cancer.