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| 題名: | LZTFL1 suppresses lung tumorigenesis by maintaining differentiation of lung epithelial cells |
| 作者: | 王陸海;Wei, Q;Chen, Z-H;Wang, L;Zhang, T;Duan, L;Behrens, C;Wistuba, I I;Minna, J D;Gao, B;Luo, J-H;Liu, Z P |
| 貢獻者: | 生醫理工學院生命科學系 |
| 關鍵詞: | 13/105;13/106;13/51;13/89;45/61;631/337;631/67/1612/1350;96/63;Animals;Apoptosis;Cancer therapies;Carcinogenesis;Carcinoma, Non-Small-Cell Lung - metabolism;Carcinoma, Non-Small-Cell Lung - pathology;Cell Biology;Cell Differentiation;Cell Line, Tumor;Cell Transformation, Neoplastic;Cellular biology;Development and progression;Down-Regulation;Epithelial Cells - pathology;Epithelial-Mesenchymal Transition;Gene expression;Genetic aspects;Health aspects;Hedgehog Proteins - metabolism;Human Genetics;Humans;Internal Medicine;Lung - pathology;Lung cancer;Lung cancer, Non-small cell;Lung Neoplasms - metabolism;Lung Neoplasms - pathology;Matrix Metalloproteinase 10 - metabolism;Medicine;Medicine & Public Health;Metastasis;Mice;Oncology;Original;original-article;Properties;Signal Transduction;Survival Analysis;Transcription factors;Transcription Factors - metabolism |
| 日期: | 2016-05-19 |
| 上傳時間: | 2026-04-23 11:13:17 (UTC+8) |
| 出版者: | Nature Publishing Group;London: Nature Publishing Group UK |
| 摘要: | 摘要： Lung cancer is the leading cause of cancer-related death in the United States, and metastatic behavior is largely responsible for this mortality. Mutations in multiple ‘driver’ oncogenes and tumor suppressors are known to contribute to the lung tumorigenesis and in some cases represent therapeutic targets. Leucine Zipper Transcription Factor-like 1 ( LZTFL1 ) is located in the chromosome region 3p21.3 where allelic loss and genetic alterations occur early and frequently in lung cancers. Previously, we found that LZTFL1 is downregulated in epithelial tumors, including lung cancer, and functions as a tumor suppressor in gastric cancers. However, the functional role of LZTFL1 in lung oncogenesis is undefined. We show here that downregulation of LZTFL1 expression in non-small cell lung cancer is associated with recurrence and poor survival, whereas re-expression of LZTFL1 in lung tumor cells inhibited extravasation/colonization of circulating tumor cells to the lung and inhibited tumor growth in vivo . Mechanistically, we found that LZTFL1 is expressed in ciliated human bronchial epithelial cells (HBECs) and its expression correlates with HBEC differentiation. LZTFL1 inhibits transforming growth factor β-activated mitogen-activated protein kinase and hedgehog signaling. Alteration of intracellular levels of LZTFL1 resulted in changes of expression of genes associated with epithelial-to-mesenchymal transition (EMT). We conclude that LZTFL1 inhibits lung tumorigenesis, possibly by maintaining epithelial cell differentiation and/or inhibition of signalings that lead to EMT and suggest that reactivation of LZTFL1 expression in tumor cells may be a novel lung cancer therapeutic approach.
其他題名： Oncogene
出版者： London: Nature Publishing Group UK
出版日期： 2016-05-19
出處： Oncogene, 2016-05, Vol.35 (20), p.2655-2663
資源來源： Springer Nature Link
版權： The Author(s) 2016
版權： COPYRIGHT 2016 Nature Publishing Group
版權： Copyright Nature Publishing Group May 19, 2016
版權： Copyright © 2016 Macmillan Publishers Limited 2016 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.2015.328
識別號： PMID: 26364604
識別號： CODEN: ONCNES |
| 顯示於類別: | [生命科學系] 期刊論文
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