https://scholars.lib.ntu.edu.tw/handle/123456789/452634
標題: | Protein tyrosine phosphatase PTPN3 inhibits lung cancer cell proliferation and migration by promoting EGFR endocytic degradation | 作者: | Li, Meng Yen Lai, Peilun Chou, Yu Ting Chi, A. P. Mi, Y. Z. Khoo, Kay-Hooi GEEN-DONG CHANG Wu, Chengwen Meng, Tzuching Chen, Guang-Chao |
公開日期: | 2015 | 卷: | 34 | 期: | 29 | 起(迄)頁: | 3791 - 3803 | 來源出版物: | Oncogene | 摘要: | Epidermal growth factor receptor (EGFR) regulates multiple signaling cascades essential for cell proliferation, growth and differentiation. Using a genetic approach, we found that Drosophila FERM and PDZ domain-containing protein tyrosine phosphatase, dPtpmeg, negatively regulates border cell migration and inhibits the EGFR/Ras/mitogen-activated protein kinase signaling pathway during wing morphogenesis. We further identified EGFR pathway substrate 15 (Eps15) as a target of dPtpmeg and its human homolog PTPN3. Eps15 is a scaffolding adaptor protein known to be involved in EGFR endocytosis and trafficking. Interestingly, PTPN3-mediated tyrosine dephosphorylation of Eps15 promotes EGFR for lipid raft-mediated endocytosis and lysosomal degradation. PTPN3 and the Eps15 tyrosine phosphorylation-deficient mutant suppress non-small-cell lung cancer cell growth and migration in vitro and reduce lung tumor xenograft growth in vivo. Moreover, depletion of PTPN3 impairs the degradation of EGFR and enhances proliferation and tumorigenicity of lung cancer cells. Taken together, these results indicate that PTPN3 may act as a tumor suppressor in lung cancer through its modulation of EGFR signaling. ? 2015 Macmillan Publishers Limited. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/452634 https://www2.scopus.com/inward/record.uri?eid=2-s2.0-84937398471&doi=10.1038%2fonc.2014.312&partnerID=40&md5=11cc0114f540e803d398b9e34320a0a8 |
ISSN: | 09509232 | DOI: | 10.1038/onc.2014.312 | SDG/關鍵字: | epidermal growth factor receptor; epidermal growth factor receptor pathway substrate 15; lentivirus vector; non receptor protein tyrosine phosphatase 3; non receptor protein tyrosine phosphatase 4; short hairpin RNA; epidermal growth factor receptor; EPS15 protein, human; non receptor protein tyrosine phosphatase 3; PTPN3 protein, human; signal transducing adaptor protein; animal cell; animal experiment; animal model; animal tissue; antiproliferative activity; Article; cancer inhibition; cell migration; cell proliferation; controlled study; drug targeting; endocytosis; human; human cell; in vitro study; in vivo study; lipid raft; lung cancer cell line; lysosome; macrophage migration inhibition; male; mouse; mutant; non small cell lung cancer; nonhuman; priority journal; protein degradation; protein dephosphorylation; protein depletion; protein expression; protein phosphorylation; signal transduction; tumor xenograft; viral gene delivery system; animal; Bagg albino mouse; cell line; cell membrane; cell motion; cell proliferation; confocal microscopy; endocytosis; female; genetics; HEK293 cell line; immunoblotting; lung tumor; metabolism; mutation; non small cell lung cancer; nude mouse; pathology; phosphorylation; RNA interference; transgenic animal; tumor cell line; xenograft; Adaptor Proteins, Signal Transducing; Animals; Animals, Genetically Modified; Carcinoma, Non-Small-Cell Lung; Cell Line; Cell Line, Tumor; Cell Movement; Cell Proliferation; Endocytosis; Female; HEK293 Cells; Humans; Immunoblotting; Lung Neoplasms; Male; Membrane Microdomains; Mice, Inbred BALB C; Mice, Nude; Microscopy, Confocal; Mutation; Phosphorylation; Protein Tyrosine Phosphatase, Non-Receptor Type 3; Receptor, Epidermal Growth Factor; RNA Interference; Transplantation, Heterologous |
顯示於: | 生化科學研究所 |
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