Plasminogen activator inhibitor-1 regulates infiltration of macrophages into melanoma via phosphorylation of FAK-Tyr925

Bikash Thapa, Bon Hun Koo, Yeon Hyang Kim, Hyung Joo Kwon, Doo Sik Kim

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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 Tyr925, 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.

Original languageEnglish
Pages (from-to)1696-1701
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume450
Issue number4
DOIs
StatePublished - Aug 8 2014
Externally publishedYes

Keywords

  • FAK
  • Invasion
  • LRP1
  • Macrophage
  • Melanoma
  • PAI-1

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