14-3-3ζ-Hsp27复合物促进非小细胞肺癌上皮间皮转化及机制的研究
批准号:
81201834
项目类别:
青年科学基金项目
资助金额:
23.0 万元
负责人:
丁建勇
依托单位:
学科分类:
H1809.肿瘤复发与转移
结题年份:
2015
批准年份:
2012
项目状态:
已结题
项目参与者:
卢春来、李懿、逄旭光、林宗武、黄威、汪灏、古杰、赵广银
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中文摘要
近年,上皮间皮转化(EMT)在肿瘤侵袭转移中的作用(包括肺癌)颇受关注。14-3-3ζ是一种可溶性酸性蛋白质,其参与多种信号转导。新近研究示其在肿瘤中过表达并与患者预后负相关;且证实其过表达在TGFβ诱导细胞EMT过程中起关键作用,其被视为一潜在的癌基因。我们前期研究发现:1高分期肺癌中14-3-3ζ表达明显高于低分期肺癌且与患者预后负相关,下调其表达可抑制细胞侵袭;2其高表达可诱导ERK1/2激活,免疫共沉淀结合质谱分析证实其与Hsp27等多种蛋白形成复合物;3在肺癌细胞中下调Hsp27表达可逆转14-3-3ζ诱导的细胞表型,如EMT。考虑到Hsp27在肿瘤中的重要作用及其功能与14-3-3ζ高度重叠,本研究拟:在肺癌组织中研究14-3-3ζ与Hsp27表达,分析两者的相关性及与患者预后关系;在细胞中研究两者表达有无相互影响及与肺癌EMT的关系;最后分子水平研究其具体机制并体内实验证实。
英文摘要
In recent years, epithelial mesothelioma transitions (EMT) in tumor invasion and metastasis (including lung cancer) is of great concern. 14-3-3ζ is a soluble acidic protein, and it participate in a variety of signal transduction. Recent studies have shown that it is overexpressed in many tumor tissues and associated with the poor patient's prognosis. Its overexpression has been reported to be involved in the TGFβ-induced EMT of tumor cells; and it has been viewed as a potential oncogene. Our previous study found that: 1 14-3-3ζ expression in high-stage lung cancer was significantly higher than those of the low-stage lung caner and negatively correlated with the prognosis of patients, and its reduced expression inhibited tumor cells invasion; 2 its overexpression can up-regulate the activation of ERK1/2, and Co-immunoprecipitation combined with mass spectrometry analysis confirmed that 14-3-3ζ form a complex with Hsp27 and the other proteins; 3 the reduction in Hsp27 expression in lung cancer cells reversed the 14-3-3ζ-induced phenotype, such as EMT. Taking into account the important role of Hsp27 in tumors and the high overlap of the function between Hsp27 and 14-3-3ζ, here, we try to explore the expression of 14-3-3ζ and Hsp27 in lung cancer and the corresponding adjacent tissues, and analyze their relevance and relationship with patients' prognosis; then we try to determine their expression in cancer cells to find the influence between them, and the relationship between their expression and lung cancer EMT; Finally, the specific signalling pathway will be studied and in vivo study will be performed.
14-3-3ζ是一种可溶性酸性蛋白质,其参与多种信号转导。新近研究示其在肿瘤中过表达并与患者预后负相关;且证实其过表达在TGFβ诱导细胞EMT 过程中起关键作用,其被视为一潜在的癌基因。我们前期研究发现:1.14-3-3ζ与Hsp27等多种蛋白形成复合物,14-3-3ζ与Hsp27复合物被免疫共沉淀后Western blot进一步证实,免疫荧光证实两者呈胞浆表达,位置重叠;2. 两组在肺癌组织中均高表达;两组在肺癌组织中表现为中度相关(r=0.605);3.在高表达14-3-3ζ或Hsp27细胞干扰Hsp27或14-3-3ζ下调细胞移动与侵袭能力,两者共同高表达,肺癌细胞侵袭能力最强;4.在肺癌组织芯片中检测14-3-3ζ与Hsp27表达,结合随访分析证实,共同高表达14-3-3ζ与Hsp27的患者预后最差。最后在组织与细胞水平,我们发现高表达14-3-3ζ与Hsp27和E-cadherin表达负相关。本研究阐述14-3-3ζ与Hsp27形成复合物促进肺癌侵袭转移。
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DOI:--
发表时间:2013
期刊:Cancer
影响因子:--
作者:Chun-Lai Lu;Zong-Wu Lin;Jing Guo;Di Ge;
通讯作者:
Overexpression of CD88 predicts poor prognosis in non-small-cell lung cancer
CD88 过度表达预示非小细胞肺癌预后不良
DOI:10.1016/j.lungcan.2013.04.020
发表时间:2013-08-01
期刊:LUNG CANCER
影响因子:5.3
作者:Gu, Jie;Ding, Jian-yong;Ge, Di
通讯作者:Ge, Di
USP7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma.
USP7 过表达预示着肺鳞状细胞癌和大细胞癌的不良预后。
DOI:10.1007/s13277-014-2773-4
发表时间:2015-03
期刊:TUMOR BIOLOGY
影响因子:--
作者:Zhao, Guang-Yin;Lin, Zong-Wu;Lu, Chun-Lai;Gu, Jie;Yuan, Yun-Feng;Xu, Feng-Kai;Liu, Rong-Hua;Ge, Di;Ding, Jian-Yong
通讯作者:Ding, Jian-Yong
The overexpression of 14-3-3zeta; and Hsp27 promotes nonndash;small cell lung cancer progression
14-3-3的过度表达
DOI:--
发表时间:2013
期刊:Cancer
影响因子:6.2
作者:Chun-Lai Lu;Zong-Wu Lin;Jing Guo;Di Ge
通讯作者:Di Ge
High level of BRD4 promotes non-small cell lung cancer progression.
高水平的BRD4促进非小细胞肺癌进展
DOI:10.18632/oncotarget.7068
发表时间:2016-02-23
期刊:Oncotarget
影响因子:--
作者:Liao YF;Wu YB;Long X;Zhu SQ;Jin C;Xu JJ;Ding JY
通讯作者:Ding JY
肿瘤微环境C5a/C5aR1信号选择性激活免疫检查点GAL-9/TIM-3诱导肺癌免疫耐受的机制研究
- 批准号:81972168
- 项目类别:面上项目
- 资助金额:55.0万元
- 批准年份:2019
- 负责人:丁建勇
- 依托单位:
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