Dachshund binds p53 to block the growth of lung adenocarcinoma cells

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...

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Vydané v:	Cancer research (Chicago, Ill.) Ročník 73; číslo 11; s. 3262
Hlavní autori:	Chen, Ke, Wu, Kongming, Cai, Shaoxin, Zhang, Wei, Zhou, Jie, Wang, Jing, Ertel, Adam, Li, Zhiping, Rui, Hallgeir, Quong, Andrew, Lisanti, Michael P, Tozeren, Aydin, Tanes, Ceylan, Addya, Sankar, Gormley, Michael, Wang, Chenguang, McMahon, Steven B, Pestell, Richard G
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 01.06.2013
Predmet:	Adenocarcinoma - genetics Adenocarcinoma - metabolism Adenocarcinoma - pathology Adenocarcinoma of Lung Animals Cell Cycle Checkpoints - physiology Cell Growth Processes - physiology Cell Line, Tumor Cyclin-Dependent Kinase Inhibitor p21 - metabolism Eye Proteins - genetics Eye Proteins - metabolism Female Genes, p53 HCT116 Cells HEK293 Cells Heterografts Humans Immunohistochemistry Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology Mice Mice, Nude Rad51 Recombinase - antagonists & inhibitors Rad51 Recombinase - metabolism SOXB1 Transcription Factors - biosynthesis SOXB1 Transcription Factors - genetics Transcription Factors - genetics Transcription Factors - metabolism Transcription, Genetic Transfection Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism
ISSN:	1538-7445, 1538-7445
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1538-7445 1538-7445
DOI:	10.1158/0008-5472.CAN-12-3191