VCAM-1 promotes colorectal cancer progression and metastasis via the RhoA/LIMK/Cofilin pathway

Vascular cell adhesion molecule-1 (VCAM-1) has been implicated in tumor progression, but its role and molecular mechanisms in colorectal cancer (CRC) remain incompletely defined. This study investigated the clinical association and functional mechanisms of VCAM-1 in CRC. Immunohistochemistry using a tissue microarray containing 90 CRC samples showed that VCAM-1 expression was higher in CRC tissues than in adjacent non-tumorous tissues. Reanalysis of the original survival dataset showed that VCAM-1 positivity was associated with better overall survival in this cohort, whereas its associations with most clinicopathological variables were not statistically significant. This survival association should be interpreted cautiously and requires validation in larger independent cohorts. In vitro, VCAM-1 knockdown in HCT116 and SW480 cells suppressed proliferation, migration, and invasion and promoted apoptosis. Mechanistically, VCAM-1 depletion inhibited RhoA/LIMK/Cofilin signaling, reduced F-actin organization and fluorescence intensity, and reversed epithelial-mesenchymal transition (EMT)-related changes; RhoA-Q63L expression partially restored downstream signaling, cytoskeletal organization, migration, and invasion. VCAM-1 also contributed to CRC cell adhesion to endothelial cells and migration in an M2 macrophage co-culture setting. In vivo, stable VCAM-1 knockdown in HCT116 cells reduced tumor growth in a subcutaneous model. In a tail-vein BLI model, the same knockdown decreased whole-body experimental colonization burden. Together, these findings suggest that VCAM-1 may promote CRC cell progression through RhoA/LIMK/Cofilin-related cytoskeletal remodeling and tumor microenvironment-associated interactions. However, the clinical prognostic direction observed in the current cohort differs from the tumor-promoting functional findings, and the prognostic and therapeutic relevance of VCAM-1 should be further evaluated in larger studies.