Unmasking carcinoma-associated fibroblasts: Key transformation player within the tumor microenvironment

Fibroblasts have gained increasing attention in tissue desmoplasia, especially in tumors. Activated fibroblasts from various sources modulate matrix composition and stiffness associated with organ fibrosis as well as tumor progression. More importantly, cancer-associated fibroblasts (CAFs) interacts with both cancer cells and other stromal cells, providing a tumor-promoting microenvironment for tumor invasion and metastasis. However, CAF biology is not fully understood due to its heterogeneity. Here, we describe the main transforming cues that contribute to CAF activation and unveil the expanding CAF heterogeneity associated with tumor progression in multiple aspects. Finally, we summarize the prospective promising and challenging stroma-targeted anti-tumor strategies.