Format

Send to

Choose Destination
Oncotarget. 2016 Dec 20;7(51):84258-84270. doi: 10.18632/oncotarget.12481.

LDB1 overexpression is a negative prognostic factor in colorectal cancer.

Author information

1
Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
2
Department of General, Gastrointestinal and Transplantation Surgery, University Hospital Heidelberg, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
3
Department of General, Gastrointestinal, Thoracic and Vascular Surgery, University Hospital Bonn, 53127 Bonn, Germany.
4
MTA TTK Lendület Cancer Biomarker Research Group, Magyar Tudósok körútja 2., H-1117, Budapest, Hungary.
5
Semmelweis University, 2nd Department of Pediatrics, Bókay u. 53-54., H-1083, Budapest, Hungary.

Abstract

BACKGROUND:

Colorectal cancer (CRC) is the third most common cancer in western countries and is driven by the Wnt signaling pathway. LIM-domain-binding protein 1 (LDB1) interacts with the Wnt signaling pathway and has been connected to malignant diseases. We therefore aimed to evaluate the role of LDB1 in CRC.

RESULTS:

Overexpression of LDB1 in CRC is associated with strikingly reduced overall and metastasis free survival in all three independent patient cohorts. The expression of LDB1 positively correlates with genes involved in the Wnt signaling pathway (CTNNB1, AXIN2, MYC and CCND1). Overexpression of LDB1 in CRC cell lines induced Wnt pathway upregulation as well as increased invasivity and proliferation. Upon separate analysis, the role of LDB1 proved to be more prominent in proximal CRC, whereas distal CRC seems to be less influenced by LDB1.

MATERIALS AND METHODS:

The expression of LDB1 was measured via RT-qPCR in 59 clinical tumor and normal mucosa samples and correlated to clinical end-points. The role of LDB1 was examined in two additional large patient cohorts from publicly available microarray and RNAseq datasets. Functional characterization was done by lentiviral overexpression of LDB1 in CRC cell lines and TOP/FOP, proliferation and scratch assays.

CONCLUSIONS:

LDB1 has a strong role in CRC progression, confirmed in three large, independent patient cohorts. The in vitro data confirm an influence of LDB1 on the Wnt signaling pathway and tumor cell proliferation. LDB1 seems to have a more prominent role in proximal CRC, which confirms the different biology of proximal and distal CRC.

KEYWORDS:

colorectal cancer; distal; ldb1; proximal; wnt signaling

PMID:
27713177
PMCID:
PMC5356660
DOI:
10.18632/oncotarget.12481
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center