title: Plasminogen activator inhibitor-1 regulates infiltration of macrophages into melanoma via phosphorylation of FAK-Tyr⁹²⁵.
abstract: 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.
authors: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, 134 Sinchon-Dong, Seodaemun-Gu, 120-749 Seoul, Republic of Korea.
authors: Bikash
authors: B
authors: Thapa
authors: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, 134 Sinchon-Dong, Seodaemun-Gu, 120-749 Seoul, Republic of Korea.
authors: Bon-Hun
authors: BH
authors: Koo
authors: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, 134 Sinchon-Dong, Seodaemun-Gu, 120-749 Seoul, Republic of Korea.
authors: Yeon Hyang
authors: YH
authors: Kim
authors: Department of Microbiology, College of Medicine, Hallym University, Gangwon-do 200-702, Republic of Korea.
authors: Hyung-Joo
authors: HJ
authors: Kwon
authors: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, 134 Sinchon-Dong, Seodaemun-Gu, 120-749 Seoul, Republic of Korea. Electronic address: dskim@yonsei.ac.kr.
authors: Doo-Sik
authors: DS
authors: Kim
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008264:Macrophages / Q000473:pathology*; D008546:Melanoma, Experimental / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D010766:Phosphorylation; D017395:Plasminogen Activator Inhibitor 1 / Q000502:physiology*; D011973:Receptors, LDL / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D017395:Plasminogen Activator Inhibitor 1; D011973:Receptors, LDL; D025521:Tumor Suppressor Proteins; D014443:Tyrosine; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: FAK; Invasion; LRP1; Macrophage; Melanoma; PAI-1