Objective: Plasminogen Activator Inhibitor-1 has an important role in the progression of cancer. Although there are many studies about the relation of Plasminogen Activator Inhibitor-1 (PAI-1) with cancer, there exists only a few about showing the relation of PAI-1 with cancer stem cells.

Materials and Methods: The purpose of this review is to explain the relation between PAI-1 and carcinogenesis and to at- tract attention to the possible role of this protein in cancer stem cell pathway in the light of literature data.

Results: Tumor development harbors various biological processes such as resisting cell death, proliferative signaling, angiogenesis, invasion, and metastasis. Cancer Stem Cells (CSCs), known as subpopulation of tumor cells, are located within the tumor tissue with a great therapeutic resistance, self-renewal capacity, potential of induction of tumor initiation and progression. Processes involved in epithelial mesenchymal transition (EMT) and extracellular matrix (ECM) are important for cancer and CSC development since EMT increases plasticity in tumor cells; therefore, they are separated from other tissues. PAI-1 is the major inhibitor of plasmin and is associated with various diseases such as cardiovascular diseases, neuronal cell loss, and progression of hallmarks of cancer. PAI-1, which has high expression levels in most cancer types, has a role in ECM remodeling and regulation of EMT. Recent studies about cancer stem cells reveal the probable importance of PAI-1 in stemness part- way.

Conclusions: These studies might be considered as a guide for therapeutic approaches that will be focused in near future.