Integrin α1 upregulation by TF:FVIIa complex promotes cervical cancer migration through PAR2-dependent MEK1/2 activation.

Abstract

Tissue factor (TF) and protease-activated receptor 2 (PAR2) have been associated with the progression of cancer, while integrins are essential for the adhesion and migration of cancer cells. This study aimed to explore the cross-talk between the TF:FVIIa complex, PAR2 signaling, and the expression of integrin α1 in cervical cancer cells. Utilizing data from The Cancer Genome Atlas (TCGA), the research examined the relationship between the TF and PAR2 genes and the integrin α1 gene (ITGA1) in reproductive cancers, revealing a positive correlation between integrin α1 expression and both TF and PAR2 genes. Analyses through Western blotting and RT-PCR demonstrated that TF:FVIIa complex transactivates PAR2, which significantly increases the phosphorylation of MEK1/2 and subsequently elevates integrin α1 expression. Inhibition of either PAR2 or MEK1/2 resulted in a decrease in the FVIIa-induced increase in integrin α1 expression. Additionally, cell migration studies indicated that elevated expression of integrin α1, mediated by the TF:FVIIa/PAR2 pathway, was linked to enhanced cell migration, which could be inhibited by blocking integrin α1. This investigation uncovers a novel signaling pathway in HeLa cells, highlighting the significance of the TF:FVIIa:PAR2 axis in modulating integrins that are vital for cancer progression, thereby offering insights for potential targeted therapeutic approaches in cancer treatment.