ABSTRACT
Serpin family E member 1 (SERPINE1), a serine proteinase inhibitor, serves as an important regulator of extracellular matrix remodeling. Emerging evidence suggests that SERPINE1 has diverse roles in cancer and is associated with poor prognosis. However, the mechanism via which SERPINE1 is induced in cancer has not been fully determined. In order to examine the molecular mechanism of SERPINE1 expression, the present study took advantage of the isogenic pair of lung cancer cells with epithelial or mesenchymal features. Using genetic perturbation and following biochemical analysis, the present study demonstrated that SERPINE1 expression was upregulated in mesenchymal lung cancer cells and promoted cellular invasiveness. Yesassociated protein (YAP)dependent SERPINE1 expression was modulated by treatment with a Rhoassociated protein kinase inhibitor, Y27632. Moreover, TGFß treatment supported YAPdependent SERPINE1 expression, and an enhanced TGFß response in mesenchymal lung cancer cells promoted SERPINE1 expression. TGFßmediated SERPINE1 expression was significantly attenuated by knockdown of YAP or transcriptional coactivator with PDZbinding motif, suggesting that crosstalk between the TGFß and YAP pathways underlies SERPINE1 expression in mesenchymal cancer cells.