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- W2000346758 abstract "MT1-MMP is a potent proinvasive and growth promoting membrane protease in cancer. The roles of MT1-MMP are mediated by its pericellular proteolysis activity. Major substrates of MT1-MMP are collagen I and other extracellular matrices. MT1-MMP also cleaves membrane proteins and modulates their biological activities in cancer progression. However, little is known about the cell surface substrates of MT1-MMP and identification of the substrates should enable a better understanding of its multiple biological functions. Therefore to identify new substrates of MT1-MMP, we purified proteins associating with MT1-MMP in human carcinoma cells and analyzed them by mass spectrometry. As results, we identified over 40 membrane proteins, and found HB-EGF is a novel component of MT1-MMP complex. MT1-MMP cleaves HB-EGF and removes the N-terminal region that is important for binding heparin. Consequently the HB-EGF processing by MT1-MMP converts it into a heparin-independent growth factor with enhanced mitogenic activity and thereby expression of both proteins co-stimulates tumor cell growth in vitro and in vivo. Furthermore ovarian ascites carcinoma cells expressed both MT1-MMP and HB-EGF at high levels and produced MT1-MMP-cleaved HB-EGF in the ascitic fluids. These data suggest that MT1-MMP acts as a regulator of cancer progression on the cell surface. Citation Format: Naohiko Koshikawa, Motoharu Seiki. Membrane type-1 matrix metalloproteinase (MT1-MMP) is a potent regulator of cancer malignant progression through the heparin-binding EGF-like growth factor activation. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C65." @default.
- W2000346758 created "2016-06-24" @default.
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- W2000346758 date "2013-02-01" @default.
- W2000346758 modified "2023-09-25" @default.
- W2000346758 title "Abstract C65: Membrane type-1 matrix metalloproteinase (MT1-MMP) is a potent regulator of cancer malignant progression through the heparin-binding EGF-like growth factor activation" @default.
- W2000346758 doi "https://doi.org/10.1158/1538-7445.tim2013-c65" @default.
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