The Role of the Plasminogen Activator Inhibitor 1 ( PAI1 ) in Ovarian Cancer: Mechanisms and Therapeutic Implications

Abstract

Ovarian cancer (OC) is one among most significantly fatal gynecological cancers, with late-stage detection and an inadequate prognosis. Plasminogen activator inhibitor-1 ( PAI1 ) gene anticipates negative outcomes in many different kinds of malignancies. Several research investigations are currently being done to examine the biological role of PAI1 in OC and the possible benefits of targeted pharmacotherapies. The PAI1 gene has been linked to the emergence and development of cancer in the ovary. PAI1 , an inhibitor of serine protease, influences the fibrinolysis and extracellular matrix remodeling, both of which are crucial for tumor expansion and metastatic growth. PAI1 levels have been discovered to be subsequently more elevated in malignant ovarian tissues than in usual ovarian tissue, demonstrating a potential connection among PAI1 overexpression and OC development. PAI1 promotes tumor cell proliferation, movement, and an invasion by influencing the urokinase-plasminogen activators and through interactions with cell surface receptors. In addition, PAI1 gene contributes to angiogenesis and apoptotic cell death, which contribute to the more hostile phenotypes of OC. The prognostic and therapeutic consequences of focusing on PAI1 in OC are explored, demonstrating PAI1 's potential to be a biomarker and emphasizing for novel treatment approaches. The PAI1 gene possesses several functions in OC, affecting tumor development, an invasion, and metastatic growth. Comprehending the complicated interactions and mechanisms that regulate PAI1 in OC may lead to more efficient evaluation and treatment strategies and ultimately enhance patient outcomes.

Keywords: OC; PAI1 gene; biomarker; metastasis; therapeutic target.

Fig. 1

The gene plasminogen activator inhibitor-1 (PAI-1) is found on chromosome 7q22.1. There are nine exons and eight introns in the PAI-1 gene. The noncoding areas of the introns are separated from the coding sequences that generate the protein in the exons. Numerous regulatory elements, including TATA and CAAT boxes, as well as binding domains for transcription factors, including Sp1, AP-1, and AP-2, which control gene expression in regard to different physiological stimuli, are present in the upstream region of the PAI-1 gene.

Fig. 2

Plasminogen activator inhibitor-1 (PAI1)-mediated signaling pathways play a role in regulating various cellular processes, particularly those related to tumorigenesis and progression. The integrin complex including urokinase-plasminogen activator (uPA), uPA receptor (uPAR), and PAI1 triggers endocytosis via lipoprotein receptor protein (LRP)-1 and very-low-density lipoprotein receptor (VLDL-R). The process finally results in the recovery of integrin, uPAR, and LRP-1 to the plasma membrane and the lysosomal destruction of the uPA and PAI1 complexes. This activation eventually promotes the invasion and proliferation of cancer cells by activating the extracellular signal-regulated kinase (ERK) pathway. Furthermore, this promotes matrix metalloproteinase's (MMP's) gene expression patterns, which aid in the invasion of cancer cells.