Epidermal Growth Factor Receptor-Mediated Membrane Type 1 Matrix Metalloproteinase Endocytosis Regulates the Transition Between Invasive Versus Expansive Growth of Ovarian Carcinoma Cells in Three-Dimensional Collagen
作者： Natalie M. Moss , Yueying Liu , Jeff J. Johnson , Philip Debiase , Jonathan Jones
DOI: 10.1158/1541-7786.MCR-08-0571
关键词: Ovarian cancer 、 Cancer research 、 Ovarian carcinoma 、 Epidermal growth factor receptor 、 Cell 、 Endocytic cycle 、 Internalization 、 Cell biology 、 Biology 、 Epidermal growth factor 、 Cell growth
摘要: The epidermal growth factor receptor (EGFR) is overexpressed in ovarian carcinomas and promotes cellular responses that contribute to cancer pathobiology. In addition modulation of mitogenic motogenic behavior, emerging data identify EGFR activation as a novel mechanism for rapid modification the cell surface proteome. transmembrane collagenase membrane type 1 matrix metalloproteinase (MT1-MMP, MMP-14) major contributor pericelluar proteolysis carcinoma microenvironment subjected extensive posttranslational regulation. present study, contribution control MT1-MMP dynamics was investigated. Unstimulated cells display caveolar colocalization MT1-MMP, whereas prompts internalization via distinct endocytic pathways. EGF treatment results phosphorylation cytoplasmic tail, expressing tyrosine mutated form (MT1-MMP-Y573F) exhibit defective internalization. As result sustained activity, phenotypic epithelial-mesenchymal transition observed, characterized by enhanced migration collagen invasion, within three-dimensional gels inhibited. These support an EGFR-dependent regulation between invasive expansive dynamics. (Mol Cancer Res 2009;7(6):809–20)
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