Pan-Cancer Analysis Reveals AEBP1–Collagen Co-Expression and Its Potential Role in CAF-Mediated Tumor Stiffness

This study investigates the role of adipocyte enhancer–binding protein 1 (AEBP1) and its encoded protein, aortic carboxypeptidase-like protein (ACLP), in regulating tumor stiffness through cancer-associated fibroblast (CAF) activity across multiple cancer types. Through integrated transcriptomic analyses of 32 TCGA tumor types, AEBP1 expression was found to correlate strongly with collagen and extracellular matrix (ECM) gene sets, particularly within the CAF compartment. Single-cell RNA-seq of breast and pancreatic tumors revealed that AEBP1 is co-expressed with collagen family genes in myofibroblastic and matrix CAFs. Functional assays using 3D oral squamous cell carcinoma (OSCC)-derived CAF spheroids demonstrated that AEBP1 knockdown markedly decreased mechanical stiffness without affecting spheroid size or morphology. Together, these findings identify AEBP1/ACLP as a pan-cancer stromal regulator that enhances ECM rigidity and immune exclusion, implicating it as a therapeutic target for tumor desmoplasia and fibrosis.