POSTN-expressing cancer-associated fibroblasts: roles in the tumor microenvironment and clinical implications

Cancer-associated fibroblasts (CAFs) are among the most abundant stromal components in the tumor microenvironment and play important roles in tumor progression, metastasis, and treatment response. Periostin (POSTN) is an extracellular matrix protein predominantly secreted by CAFs. Accumulating studies have demonstrated that POSTN + CAFs participate in multiple biological processes of tumors, encompassing extracellular matrix remodeling, tumor cell invasion, angiogenesis, and regulation of immune cell function. Through crosstalk with tumor cells and diverse stromal components, POSTN + CAFs mediate the establishment of a pro-tumorigenic microenvironment and can modulate tumor therapeutic responses. Moreover, increased POSTN expression in tumor tissues has been associated with poor prognosis in various malignancies, suggesting the potential utility of POSTN as a biomarker. However, several critical scientific questions remain to be elucidated, including the origin and plasticity of POSTN + CAFs, their relationship with other CAF subsets, and the feasibility of targeting POSTN + CAFs therapeutically. Notably, POSTN + CAFs may represent a reversible fibroblast state rather than an innately determined cell lineage. In this review, we discuss the biological features and functional significance of POSTN + CAFs in cancer, emphasizing their roles in shaping the tumor microenvironment and their potential implications for clinical practice. We further discuss current challenges and future opportunities for targeting this distinct functionally defined fibroblast state, while noting that its identity as a discrete cell population remains to be established.