title: Translationally controlled tumor protein induces human breast epithelial cell transformation through the activation of Src.
abstract: Translationally controlled tumor protein (TCTP) is implicated in cell growth and malignant transformation. TCTP has been found to interact directly with the third cytoplasmic domain of the α subunit of Na,K-ATPase, but whether this interaction has a role in tumorigenesis is unclear. In this study, we examined TCTP-induced tumor progression signaling networks in human breast epithelial cells, using adenoviral infection. We found that TCTP (a) induces Src release from Na,K-ATPase α subunit and Src activation; (b) phosphorylates tyrosine residues 845, 992, 1086, 1148 and 1173 on anti-epidermal growth factor receptor (EGFR); (c) activates PI3K (phosphatidylinositol 3-kinase )-AKT, Ras-Raf-MEK-ERK1/2, Rac-PAK1/2, MKK3/6-p38 and phospholipase C (PLC)-γ pathways; (d) enhances NADPH oxidase-dependent reactive oxygen species (ROS) generation; (e) stimulates cytoskeletal remodeling and cell motility and (f) upregulates matrix metalloproteinase (MMP) 3 and 13. These findings suggest that TCTP induces tumorigenesis through distinct multicellular signaling pathways involving Src-dependent EGFR transactivation, ROS generation and MMP expression.
authors.affiliation: College of Pharmacy, Center for Cell Signalling & Drug Discovery Research, Ewha Womans University, Seoul, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Jung
authors.forename: H Y
authors.initials: HY
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Kim
authors.forename: K
authors.initials: K
authors.lastname: Sohn
authors.forename: M
authors.initials: M
authors.lastname: Kim
authors.forename: K
authors.initials: K
authors.lastname: Lee
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D014158:Transcription, Genetic; D000090324:Tumor Protein, Translationally-Controlled 1; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; D019255:NADPH Oxidases; D066246:ErbB Receptors; D019061:src-Family Kinases