Plasminogen activator inhibitor-1 regulates infiltration of macrophages into melanoma via phosphorylation of FAK-Tyr⁹²⁵.
Tumor-infiltrating macrophages are potential candidates for cancer immunotherapy. However, the detailed molecular mechanism underlying macrophage infiltration into tumors is poorly understood. Based on our previous finding that plasminogen activator inhibitor-1 (PAI-1) enhances vitronectin-dependent migration of macrophages, we investigated the potential role of PAI-1 in macrophage invasion into melanoma. Experimental evidence obtained from spheroid confrontation assay clearly showed that PAI-1 overexpression significantly enhanced the invasion of RAW 264.7 cells into B16F10 melanoma. We further demonstrated that PAI-1 induces phosphorylation of focal adhesion kinase (FAK) at Tyr(925), which, in turn, mediated the invasion of macrophages into the melanoma. This work further illustrates that low-density lipoprotein receptor related-protein 1 (LRP1) is essential for PAI-1-mediated FAK phosphorylation and macrophage invasion into melanoma. In conclusion, our study demonstrates a novel role of PAI-1 in macrophage invasion into melanoma and provides insights into the underlying molecular mechanism.
['Thapa|Bikash|B|', 'Koo|Bon-Hun|BH|', 'Kim|Yeon Hyang|YH|', 'Kwon|Hyung-Joo|HJ|', 'Kim|Doo-Sik|DS|']
D000818:Animals D001483:Base Sequence D002460:Cell Line D017931:DNA Primers D051416:Focal Adhesion Protein-Tyrosine Kinases D026503:Low Density Lipoprotein Receptor-Related Protein-1 D008264:Macrophages D008546:Melanoma, Experimental D051379:Mice D010766:Phosphorylation D017395:Plasminogen Activator Inhibitor 1 D011973:Receptors, LDL D025521:Tumor Suppressor Proteins D014443:Tyrosine
Macrophage Melanoma PAI-1 Invasion FAK LRP1