The C-terminus of ephrin-B1 regulates metalloproteinase secretion and invasion of cancer cells.
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| Abstract |
Interaction of the Eph family of receptor protein tyrosine kinases and their ligands, ephrin family members, induces bi-directional signaling via cell-cell contacts. High expression of B-type ephrin is associated with high invasion potential of tumors, however, the mechanism by which ephrin-B promotes cancer cell invasion is poorly understood. We show that interaction of ephrin-B1 with the Eph receptor B2 (EphB2) significantly enhances processing of the extracellular domain of ephrin-B1, which is regulated by the C-terminus. Matrix metalloproteinase-8 (MMP-8) is the key protease that cleaves ephrin-B1, and the C-terminus of ephrin-B1 regulates activation of the extracellular release of MMP-8 without requirement of de novo protein synthesis. One possible mechanism by which ephrin-B1 regulates the exocytosis of MMP-8 is the activation of Arf1 GTPase, a critical regulator of membrane trafficking. In support of this hypothesis, activation of ephrin-B1 increased GTP-bound Arf1, and the secretion of MMP-8 was reduced by expression of a dominant-negative mutant of Arf1. Expression of ephrin-B1 promoted the invasion of cancer cells in vivo, which required the C-terminus of ephrin-B1. Our results suggest a novel function of the C-terminus of ephrin-B1 in activating MMP-8 secretion, which promotes the invasion of cancer cells.
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| Authors | Masamitsu Tanaka, Kazuki Sasaki, Reiko Kamata, Ryuichi Sakai |
| Journal | Journal of cell science (J Cell Sci) Vol. 120 Issue Pt 13 Pg. 2179-89 (Jul 01 2007) ISSN: 0021-9533 [Print] England |
| PMID | 17567680 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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