Emerging role of cancer-associated fibroblasts in the premetastatic niche

In recent years, tumor metastasis has become one of the major causes of high recurrence and mortality in cancer patients. Owing to multiorgan involvement, metastatic cancers are now clinically difficult to cure and often have a very poor prognosis. In recent years, an increasing number of studies have shown that the establishment of a premetastatic niche (PMN) is necessary for tumor metastasis. Cancer-associated fibroblasts (CAFs), which are closely related to tumor development, are deeply involved in regulating PMN establishment. By regulating EVs, metabolism and other pathways, CAFs actively shape microenvironmental characteristics, including inflammation, angiogenesis, increased vascular permeability, lymphangiogenesis, immunosuppression and extracellular matrix (ECM) remodeling. With the development of single-cell sequencing technology, our understanding of the role and significance of heterogeneous CAFs in the PMN has improved. Multiple therapeutic strategies targeting CAFs in the PMN have also been developed. This article focuses on the crosstalk of different subtypes of CAFs with other stromal cells, the mechanisms by which CAFs of different origins mediate PMN formation, and the emerging cancer therapeutic strategies by which CAFs have been targeted in recent years.