Dachshund Binds p53 to Block the Growth of Lung Adenocarcinoma Cells

被引：53

作者：

Chen, Ke ^{[1
,3
]}

Wu, Kongming ^{[1
,3
]}

Cai, Shaoxin ^{[1
,3
]}

Zhang, Wei ^{[1
,3
]}

Zhou, Jie ^{[1
,3
]}

Wang, Jing ^{[1
,3
]}

Ertel, Adam ^{[1
,3
]}

Li, Zhiping ^{[1
,3
]}

Rui, Hallgeir ^{[1
]}

Quong, Andrew ^{[1
]}

Lisanti, Michael P. ^{[2
,3
]}

Tozeren, Aydin ^{[3
,4
,5
]}

Tanes, Ceylan ^{[3
,4
,5
]}

Addya, Sankar ^{[1
,3
]}

Gormley, Michael ^{[1
,3
]}

Wang, Chenguang ^{[1
,2
,3
]}

McMahon, Steven B. ^{[1
,3
]}

Pestell, Richard G. ^{[1
,3
]}

机构：

[1] Thomas Jefferson Univ, Dept Canc Biol, Philadelphia, PA 19107 USA

[2] Thomas Jefferson Univ, Dept Stem Cell Biol & Regenerat Med, Philadelphia, PA 19107 USA

[3] Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA

[4] Drexel Univ, Ctr Integrated Bioinformat, Philadelphia, PA 19104 USA

[5] Drexel Univ, Sch Biomed Engn Syst & Hlth Sci, Philadelphia, PA 19104 USA

来源：

CANCER RESEARCH | 2013年 / 73卷 / 11期

关键词：

FATE DETERMINATION FACTOR; CYCLIN D1; BREAST-CANCER; DACH1; GENE; TRANSCRIPTION; EXPRESSION;

D O I：

10.1158/0008-5472.CAN-12-3191

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Hyperactive EGF receptor (EGFR) and mutant p53 are common genetic abnormalities driving the progression of non-small cell lung cancer (NSCLC), the leading cause of cancer deaths in the world. The Drosophila gene Dachshund (Dac) was originally cloned as an inhibitor of hyperactive EGFR alleles. Given the importance of EGFR signaling in lung cancer etiology, we examined the role of DACH1 expression in lung cancer development. DACH1 protein and mRNA expression was reduced in human NSCLC. Reexpression of DACH1 reduced NSCLC colony formation and tumor growth in vivo via p53. Endogenous DACH1 colocalized with p53 in a nuclear, extranucleolar location, and shared occupancy of -15% of p53-bound genes in ChIP sequencing. The C-terminus of DACH1 was necessary for direct p53 binding, contributing to the inhibition of colony formation and cell-cycle arrest. Expression of the stem cell factor SOX2 was repressed by DACH1, and SOX2 expression was inversely correlated with DACH1 in NSCLC. We conclude that DACH1 binds p53 to inhibit NSCLC cellular growth. (C) 2013 AACR.

引用

页码：3262 / 3274

页数：13

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