MCT-1 expression and PTEN deficiency synergistically promote neoplastic multinucleation through the Src/p190B signaling activation

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題名:	MCT-1 expression and PTEN deficiency synergistically promote neoplastic multinucleation through the Src/p190B signaling activation
作者:	王陸海;Wu, M-H;Chen, Y-A;Chen, H-H;Chang, K-W;Chang, I-S;Wang, L-H;Hsu, H-L
貢獻者:	生醫理工學院生命科學系
關鍵詞:	13;13/1;13/105;14;14/19;38;38/109;38/77;45;49;631/326/171;64;64/60;82;82/51;96;96/95;Animals;Apoptosis;Breast cancer;Breast Neoplasms - genetics;Breast Neoplasms - pathology;Cell Biology;Cell Line, Tumor;Cell Nucleus - metabolism;Cellular signal transduction;Female;Gene expression;Gene Expression Regulation, Neoplastic;Genetic aspects;GTPase-Activating Proteins - metabolism;Health aspects;Human Genetics;Humans;Internal Medicine;MCF-7 Cells;Medicine;Medicine & Public Health;Mice;Oncogene Proteins - genetics;Oncogene Proteins - metabolism;Oncogenes;Oncology;Original;original-article;Physiological aspects;Proto-Oncogene Proteins pp60(c-src) - metabolism;PTEN Phosphohydrolase - genetics;PTEN Phosphohydrolase - metabolism;rhoA GTP-Binding Protein - metabolism;Signal Transduction;Tumors
日期:	2014-10-23
上傳時間:	2026-04-23 11:13:18 (UTC+8)
出版者:	Nature Publishing Group;London: Nature Publishing Group UK
摘要:	摘要： Multinucleation is associated with malignant neoplasms; however, the molecular mechanism underlying the nuclear abnormality remains unclear. Loss or mutation of PTEN promotes the development of malignant tumors. We now demonstrate that increased expression of the oncogene MCT-1 ( m ultiple c opies in T -cell malignancy 1) antagonizes PTEN gene presentation, PTEN protein stability and PTEN functional activity, thereby further promoting phosphoinositide 3 kinase/AKT signaling, survival rate and malignancies of the PTEN-deficient cells. In the PTEN-null cancer cells, MCT-1 interacts with p190B and Src in vivo , supporting that they are in proximity of the signaling complexes. MCT-1 overexpression and PTEN loss synergistically augments the Src/p190B signaling function that leads to inhibition of RhoA activity. Under such a condition, the incidence of mitotic catastrophes including spindle multipolarity and cytokinesis failure is enhanced, driving an Src/p190B/RhoA-dependent neoplastic multinucleation. Targeting MCT-1 by the short hairpin RNA markedly represses the Src/p190B function, improves nuclear structures and suppresses xenograft tumorigenicity of the PTEN-null breast cancer cells. Consistent with the oncogenic effects in vitro , clinical evidence has confirmed that MCT-1 gene stimulation is correlated with p190B gene promotion and PTEN gene suppression in human breast cancer. Accordingly, MCT-1 gene induction is recognized as a potential biomarker of breast tumor development. Abrogating MCT-1 function may be a promising stratagem for management of breast cancer involving Src hyperactivation and/or PTEN dysfunction. 其他題名： Oncogene 出版者： London: Nature Publishing Group UK 出版日期： 2014-10-23 出處： Oncogene, 2014-10, Vol.33 (43), p.5109-5120 資源來源： EBSCOhost Academic Search Premier 版權： The Author(s) 2014 版權： COPYRIGHT 2014 Nature Publishing Group 版權： Copyright Nature Publishing Group Oct 23, 2014 版權： Copyright © 2014 Macmillan Publishers Limited 2014 Macmillan Publishers Limited 識別號： ISSN: 0950-9232 識別號： ISSN: 1476-5594 識別號： EISSN: 1476-5594 識別號： DOI: 10.1038/onc.2014.125 識別號： PMID: 24858043 識別號： CODEN: ONCNES
顯示於類別:	[生命科學系] 期刊論文

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