期刊
ONCOGENE
卷 30, 期 19, 页码 2264-2274出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2010.604
关键词
Na; K-ATPase; Src; TCTP; tumorigenesis
资金
- Ministry for Health, Welfare Family Affairs [A090030]
- Korean Government [2009-0064401]
- MEST [R01-2007-000-20263-0]
- Seoul RBD Program [ST090801]
- MOST/KOSEF [R15-2006-020]
- Korea Health Promotion Institute [A090030] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [R01-2007-000-20263-0, 2009-0064401, 2010-0007002] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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 alpha 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 alpha 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)-gamma 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. Oncogene (2011) 30, 2264-2274; doi:10.1038/onc.2010.604; published online 31 January 2011
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