IR@PKUHSC  > 北京大学第一临床医学院  > 消化科
学科主题临床医学
SchA-p85-FAK complex dictates isoform-specific activation of Akt2 and subsequent PCBP1-mediated post-transcriptional regulation of TGF beta-mediated epithelial to mesenchymal transition in human lung cancer cell line A549
Xue, Xinying1,6; Wang, Xin7; Liu, Yuxia2,3; Teng, Guigen4; Wang, Yong1; Zang, Xuefeng5; Wang, Kaifei6; Zhang, Jinghui1; Xu, Yali1; Wang, Jianxin6; Pan, Lei1
关键词Lung Cancer Emt Tgf-beta Pcbp1 Ilei Dab2 Akt2
刊名TUMOR BIOLOGY
2014-08-01
DOI10.1007/s13277-014-1982-1
35期:8页:7853-7859
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
资助者Study on Railway Workers Chronic Disease Management Network Information Platform ; Study on Railway Workers Chronic Disease Management Network Information Platform
研究领域[WOS]Oncology
关键词[WOS]PROTEINS ; SHC ; IDENTIFICATION ; RESIDUES ; RECEPTOR ; SUBUNIT ; BINDING ; P85
英文摘要

A post-transcriptional pathway by which TGF-beta modulates expression of specific proteins, Disabled-2 (Dab2) and Interleukin-like EMT Inducer (ILEI), inherent to epithelial to mesenchymal transition (EMT) in murine epithelial cells through Akt2-mediated phosphorylation of poly r(C) binding protein (PCBP1), has been previously elucidated. The aims of the current study were to determine if the same mechanism is operative in the non-small cell lung cancer (NSCLC) cell line, A549, and to delineate the underlying mechanism. Steady-state transcript and protein expression levels of Dab2 and ILEI were examined in A549 cells treated with TGF-beta for up to 48 h. Induction of translational de-repression in this model was quantified by polysomal fractionation followed by qRT-PCR. The underlying mechanism of isoform-specific activation of Akt2 was elucidated through a combination of co-immunoprecipitation studies. TGF-beta induced EMT in A549 cells concomitant with translational upregulation of Dab2 and ILEI proteins through isoform-specific activation of Akt2 followed by phosphorylation of PCBP1 at serine-43. Our experiments further elucidated that the adaptor protein SchA is phosphorylated at tyrosine residues following TGF-beta treatment, which initiated a signaling cascade resulting in the sequential recruitment of p85 subunit of PI3K and focal adhesion kinase (FAK). The SchA-FAK-p85 complex subsequently selectively recruited and activated Akt2, not Akt1. Inhibition of the p85 subunit through phosphorylated 1257 peptide completely attenuated EMT in these cells. We have defined the underlying mechanism responsible for isoform-specific recruitment and activation of Akt2, not Akt1, during TGF-beta-mediated EMT in A549 cells. Inhibition of the formation of this complex thus represents an important and novel therapeutic target in metastatic lung carcinoma.

语种英语
所属项目编号2013Z003-C
资助者Study on Railway Workers Chronic Disease Management Network Information Platform ; Study on Railway Workers Chronic Disease Management Network Information Platform
WOS记录号WOS:000341883500074
Citation statistics
Cited Times:11[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55198
Collection北京大学第一临床医学院_消化科
作者单位1.Capital Med Univ, Dept Special Med Treatment Resp Dis, Beijing Shijitan Hosp, Beijing, Peoples R China
2.Peking Union Med Coll, Res Dept, Peking Union Med Collage Hosp, Beijing 100021, Peoples R China
3.Chinese Acad Med Sci, Beijing 100730, Peoples R China
4.Peking Univ, Dept Gastroenterol, Hosp 1, Beijing 100871, Peoples R China
5.Capital Med Univ, Dept Crit Care Med, Beijing Shijitan Hosp, Beijing, Peoples R China
6.Chinese Peoples Liberat Army Gen Hosp, Dept Resp Dis, Beijing, Peoples R China
7.Tianjin Fifth Cent Hosp, Dept Endocrinol Dis, Tianjin, Peoples R China
Recommended Citation
GB/T 7714
Xue, Xinying,Wang, Xin,Liu, Yuxia,et al. SchA-p85-FAK complex dictates isoform-specific activation of Akt2 and subsequent PCBP1-mediated post-transcriptional regulation of TGF beta-mediated epithelial to mesenchymal transition in human lung cancer cell line A549[J]. TUMOR BIOLOGY,2014,35(8):7853-7859.
APA Xue, Xinying.,Wang, Xin.,Liu, Yuxia.,Teng, Guigen.,Wang, Yong.,...&Pan, Lei.(2014).SchA-p85-FAK complex dictates isoform-specific activation of Akt2 and subsequent PCBP1-mediated post-transcriptional regulation of TGF beta-mediated epithelial to mesenchymal transition in human lung cancer cell line A549.TUMOR BIOLOGY,35(8),7853-7859.
MLA Xue, Xinying,et al."SchA-p85-FAK complex dictates isoform-specific activation of Akt2 and subsequent PCBP1-mediated post-transcriptional regulation of TGF beta-mediated epithelial to mesenchymal transition in human lung cancer cell line A549".TUMOR BIOLOGY 35.8(2014):7853-7859.
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