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Tytuł pozycji:

LDB1 overexpression is a negative prognostic factor in colorectal cancer.

Tytuł :
LDB1 overexpression is a negative prognostic factor in colorectal cancer.
Autorzy :
García SA; Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.; Department of General, Gastrointestinal and Transplantation Surgery, University Hospital Heidelberg, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Swiersy A; Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
Radhakrishnan P; Department of General, Gastrointestinal and Transplantation Surgery, University Hospital Heidelberg, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Branchi V; Department of General, Gastrointestinal, Thoracic and Vascular Surgery, University Hospital Bonn, 53127 Bonn, Germany.
Kanth Nanduri L; Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
Győrffy B; MTA TTK Lendület Cancer Biomarker Research Group, Magyar Tudósok körútja 2., H-1117, Budapest, Hungary.; Semmelweis University, 2nd Department of Pediatrics, Bókay u. 53-54., H-1083, Budapest, Hungary.
Betzler AM; Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
Bork U; Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.; Department of General, Gastrointestinal and Transplantation Surgery, University Hospital Heidelberg, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Kahlert C; Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.; Department of General, Gastrointestinal and Transplantation Surgery, University Hospital Heidelberg, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Reißfelder C; Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.; Department of General, Gastrointestinal and Transplantation Surgery, University Hospital Heidelberg, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Rahbari NN; Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.; Department of General, Gastrointestinal and Transplantation Surgery, University Hospital Heidelberg, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Weitz J; Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.; Department of General, Gastrointestinal and Transplantation Surgery, University Hospital Heidelberg, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Schölch S; Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.; Department of General, Gastrointestinal and Transplantation Surgery, University Hospital Heidelberg, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
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Źródło :
Oncotarget [Oncotarget] 2016 Dec 20; Vol. 7 (51), pp. 84258-84270.
Typ publikacji :
Journal Article
Język :
English
Imprint Name(s) :
Original Publication: Albany, N.Y. : Impact Journals
MeSH Terms :
Gene Expression Regulation, Neoplastic*
Colorectal Neoplasms/*genetics
DNA-Binding Proteins/*genetics
LIM Domain Proteins/*genetics
Transcription Factors/*genetics
Wnt Signaling Pathway/*genetics
Cell Line, Tumor ; Cell Proliferation/genetics ; Cohort Studies ; Colorectal Neoplasms/pathology ; Disease Progression ; Female ; Gene Expression Profiling ; HCT116 Cells ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis
References :
EMBO Rep. 2003 Dec;4(12):1132-7. (PMID: 14647207)
Dis Colon Rectum. 2010 Jan;53(1):57-64. (PMID: 20010352)
Int J Oncol. 2010 Sep;37(3):707-18. (PMID: 20664940)
Science. 1998 Sep 4;281(5382):1509-12. (PMID: 9727977)
Int J Biol Sci. 2009 Oct 30;5(7):686-94. (PMID: 19918297)
J Biol Chem. 2011 Mar 25;286(12 ):10396-410. (PMID: 21285348)
Cell. 2012 Jun 8;149(6):1245-56. (PMID: 22682247)
Proc Natl Acad Sci U S A. 1999 May 11;96(10):5522-7. (PMID: 10318916)
Ann Surg. 2016 Feb;263(2):345-52. (PMID: 26501709)
Am J Pathol. 1999 Feb;154(2):515-23. (PMID: 10027409)
Nature. 2012 Jul 18;487(7407):330-7. (PMID: 22810696)
Oncogene. 2013 Sep 26;32(39):4675-82. (PMID: 23085758)
Development. 2003 Feb;130(3):495-505. (PMID: 12490556)
Genes Chromosomes Cancer. 2010 Aug;49(8):746-59. (PMID: 20544848)
Langenbecks Arch Surg. 2012 Apr;397(4):535-42. (PMID: 22350614)
Eur J Histochem. 2016 Feb 09;60(1):2536. (PMID: 26972709)
Oncotarget. 2015 Mar 10;6(7):4663-76. (PMID: 25609199)
PLoS Genet. 2014 Jul 31;10(7):e1004520. (PMID: 25079073)
Br J Cancer. 2015 Apr 14;112(8):1306-13. (PMID: 25867263)
Lancet. 2005 Jan 8-14;365(9454):153-65. (PMID: 15639298)
Nat Rev Drug Discov. 2006 Dec;5(12):997-1014. (PMID: 17139285)
Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15418-23. (PMID: 9860983)
Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14452-7. (PMID: 11734645)
Cell. 1997 Mar 21;88(6):789-99. (PMID: 9118222)
J Hepatol. 2010 Dec;53(6):1078-84. (PMID: 20828852)
Cancer Res. 2014 Mar 15;74(6):1694-704. (PMID: 24599131)
Oncotarget. 2016 Aug 2;7(31):49322-49333. (PMID: 27384994)
Cancer J. 2010 May-Jun;16(3):196-201. (PMID: 20526096)
Ann Oncol. 2014 Oct;25(10):1995-2001. (PMID: 25057166)
CA Cancer J Clin. 2016 Jan-Feb;66(1):7-30. (PMID: 26742998)
Genes Dev. 1997 Jun 1;11(11):1370-80. (PMID: 9192866)
Mol Cell Biol. 2002 Feb;22(4):1184-93. (PMID: 11809809)
EMBO J. 1991 Jan;10(1):123-32. (PMID: 1989880)
Oncotarget. 2016 May 10;7(19):27232-42. (PMID: 27029058)
Br J Cancer. 2003 May 19;88(10):1543-8. (PMID: 12771919)
Breast Cancer Res Treat. 2013 Jul;140(2):219-32. (PMID: 23836010)
Development. 1999 Oct;126(19):4247-55. (PMID: 10477293)
Development. 1997 Aug;124(15):2997-3005. (PMID: 9247341)
Contributed Indexing :
Keywords: colorectal cancer; distal; ldb1; proximal; wnt signaling
Substance Nomenclature :
0 (DNA-Binding Proteins)
0 (LDB1 protein, human)
0 (LIM Domain Proteins)
0 (Transcription Factors)
Entry Date(s) :
Date Created: 20161008 Date Completed: 20180306 Latest Revision: 20181113
Update Code :
20210210
PubMed Central ID :
PMC5356660
DOI :
10.18632/oncotarget.12481
PMID :
27713177
Czasopismo naukowe
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.

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