Dachshund binds p53 to block the growth of lung adenocarcinoma cells.
Publication/Presentation Date
6-1-2013
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.
Volume
73
Issue
11
First Page
3262
Last Page
3274
ISSN
1538-7445
Published In/Presented At
Chen, K., Wu, K., Cai, S., Zhang, W., Zhou, J., Wang, J., Ertel, A., Li, Z., Rui, H., Quong, A., Lisanti, M. P., Tozeren, A., Tanes, C., Addya, S., Gormley, M., Wang, C., McMahon, S. B., & Pestell, R. G. (2013). Dachshund binds p53 to block the growth of lung adenocarcinoma cells. Cancer research, 73(11), 3262–3274. https://doi.org/10.1158/0008-5472.CAN-12-3191
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
23492369
Department(s)
Administration and Leadership
Document Type
Article