Paranitharan Nagarajan, Kataria Shivangi, Arumugam Vijaya Anand, Hsieh Hsi-Lung, Muthukrishnan Saradhadevi, Velayuthaprabhu Shanmugam
Department of Biotechnology, Bharathiar University, Coimbatore, India.
Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore, India.
Biochem Biophys Res Commun. 2025 Jan;742:151151. doi: 10.1016/j.bbrc.2024.151151. Epub 2024 Dec 5.
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.
组织因子（TF）和蛋白酶激活受体2（PAR2）与癌症进展相关，而整合素对于癌细胞的黏附和迁移至关重要。本研究旨在探索TF:FVIIa复合物、PAR2信号传导与宫颈癌细胞中整合素α1表达之间的相互作用。利用来自癌症基因组图谱（TCGA）的数据，该研究调查了生殖系统癌症中TF和PAR2基因与整合素α1基因（ITGA1）之间的关系，发现整合素α1表达与TF和PAR2基因均呈正相关。通过蛋白质印迹法和逆转录-聚合酶链反应（RT-PCR）分析表明，TF:FVIIa复合物可反式激活PAR2，这显著增加了MEK1/2的磷酸化，进而提高了整合素α1的表达。抑制PAR2或MEK1/2会导致FVIIa诱导的整合素α1表达增加受到抑制。此外，细胞迁移研究表明，由TF:FVIIa/PAR2途径介导的整合素α1表达升高与细胞迁移增强有关，而阻断整合素α1可抑制这种迁移。本研究揭示了HeLa细胞中的一条新信号通路，强调了TF:FVIIa:PAR2轴在调节对癌症进展至关重要的整合素方面的重要性，从而为癌症治疗中的潜在靶向治疗方法提供了见解。
