Mechanistic role of the ILK‑S100A4 axis in modulating invasion and EMT in salivary adenoid cystic carcinoma

Salivary adenoid cystic carcinoma (SACC) is a prevalent malignant tumor of the salivary glands, characterized by invasive growth and perineural invasion, resulting in high rates of local recurrence, distant metastasis and poor long-term survival. Thus, elucidating the molecular mechanisms underlying SACC invasion and identifying effective therapeutic targets are of clinical importance. Functional cellular assays including proliferation, migration, and flow cytometry, and molecular experiments, such as western blot, were conducted <i>in vitro</i> to explore the effects of integrin-linked kinase (ILK) knockdown on the biological behavior of SACC cells and the expression of epithelial-mesenchymal transition (EMT) markers. Transcriptome sequencing identified S100 calcium-binding protein A4 (S100A4) as a key downstream effector regulated by ILK. Additionally, 52 clinical SACC specimens were analyzed to evaluate the correlation between S100A4 expression and clinicopathological features, as well as ILK expression. Rescue experiments validated the role of S100A4 in mediating the effects of ILK. ILK knockdown significantly suppressed the malignant behavior of SACC cells, including migration and invasion, and reversed EMT phenotypes. S100A4 expression was significantly associated with clinical features such as clinical stage and perineural invasion, along with ILK expression. Overexpression of S100A4 restored Snail expression, promoted the EMT process and rescued the impaired migration and invasion capabilities of SACC cells caused by ILK knockdown. ILK may facilitate EMT-mediated invasion in SACC cells via the Glycogen synthase kinase-3 β) signaling pathway by modulating the transcription factor Snail. S100A4 may contribute to this mechanism by modulating Snail protein. These findings imply that simultaneously targeting both ILK and S100A4 represents a novel and promising therapeutic strategy to suppress SACC progression.