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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Dachshund Binds p53 to Block the Growth of Lung Adenocarcinoma Cells
Cancer research (Chicago, Ill.), v 73(11), pp 3262-3274
01 Jun 2013
PMID: 23492369
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
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Details
- Title
- Dachshund Binds p53 to Block the Growth of Lung Adenocarcinoma Cells
- Creators
- Ke Chen - Thomas Jefferson UniversityKongming Wu - Thomas Jefferson UniversityShaoxin Cai - Thomas Jefferson UniversityWei Zhang - Thomas Jefferson UniversityJie Zhou - Kimmel Cancer CenterJing Wang - Thomas Jefferson UniversityAdam Ertel - Thomas Jefferson UniversityZhiping Li - Kimmel Cancer CenterHallgeir Rui - Thomas Jefferson UniversityAndrew Quong - Thomas Jefferson UniversityMichael P. Lisanti - Thomas Jefferson UniversityAydin Tozeren - Drexel UniversityCeylan Tanes - Drexel UniversitySankar Addya - Thomas Jefferson UniversityMichael Gormley - Thomas Jefferson UniversityChenguang Wang - Thomas Jefferson UniversitySteven B. McMahon - Thomas Jefferson UniversityRichard G. Pestell - Thomas Jefferson University
- Publication Details
- Cancer research (Chicago, Ill.), v 73(11), pp 3262-3274
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 13
- Grant note
- W81XWH- 11-1-0303 / Department of Defense Concept Award; United States Department of Defense P30CA56036 / Kimmel Cancer Center NIH Cancer Center Core grant P30CA056036 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Dr. Ralph and Marian C. Falk Medical Research Trust Pennsylvania Department of Health Thomas Jefferson University Margaret Q. Landenberger Research Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; [Retired Faculty]
- Web of Science ID
- WOS:000319736800008
- Scopus ID
- 2-s2.0-84878553762
- Other Identifier
- 991019168694904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology