LDB1 overexpression is a negative prognostic factor in colorectal cancer

• Verfasst von: García, Sebastián [VerfasserIn]
• Verfasst von: Swiersy, Anka [VerfasserIn]
• Verfasst von: Radhakrishnan, Praveen [VerfasserIn]
• Verfasst von: Branchi, Vittorio [VerfasserIn]
• Verfasst von: Kanth Nanduri, Lahiri [VerfasserIn]
• Verfasst von: Győrffy, Balázs [VerfasserIn]
• Verfasst von: Betzler, Alexander M. [VerfasserIn]
• Verfasst von: Bork, Ulrich [VerfasserIn]
• Verfasst von: Kahlert, Christoph [VerfasserIn]
• Verfasst von: Reißfelder, Christoph [VerfasserIn]
• Verfasst von: Rahbari, Nuh Nabi [VerfasserIn]
• Verfasst von: Weitz, Jürgen [VerfasserIn]
• Verfasst von: Schölch, Sebastian [VerfasserIn]
• Titel: LDB1 overexpression is a negative prognostic factor in colorectal cancer
• Verf.angabe: Sebastián A. García, Anka Swiersy, Praveen Radhakrishnan, Vittorio Branchi, Lahiri Kanth Nanduri, Balázs Győrffy, Alexander M. Betzler, Ulrich Bork, Christoph Kahlert, Christoph Reißfelder, Nuh N. Rahbari, Jürgen Weitz, Sebastian Schölch
• E-Jahr: 2016
• Jahr: October 05, 2016
• Umfang: 13 S.
• Fussnoten: Gesehen am 12.05.2020
• Titel Quelle: Enthalten in: OncoTarget
• Ort Quelle: [Erscheinungsort nicht ermittelbar] : Impact Journals LLC, 2010
• Jahr Quelle: 2016
• Band/Heft Quelle: 7(2016), 51, Seite 84258-84270
• ISSN Quelle: 1949-2553
• DOI: doi:10.18632/oncotarget.12481
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Cell Line, Tumor
• Sach-SW: Cell Proliferation
• Sach-SW: Cohort Studies
• Sach-SW: colorectal cancer
• Sach-SW: Colorectal Neoplasms
• Sach-SW: Disease Progression
• Sach-SW: distal
• Sach-SW: DNA-Binding Proteins
• Sach-SW: Female
• Sach-SW: Gene Expression Profiling
• Sach-SW: Gene Expression Regulation, Neoplastic
• Sach-SW: HCT116 Cells
• Sach-SW: Humans
• Sach-SW: Kaplan-Meier Estimate
• Sach-SW: ldb1
• Sach-SW: LIM Domain Proteins
• Sach-SW: Male
• Sach-SW: Middle Aged
• Sach-SW: Prognosis
• Sach-SW: proximal
• Sach-SW: Transcription Factors
• Sach-SW: wnt signaling
• Sach-SW: Wnt Signaling Pathway
• K10plus-PPN: 1698060440

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.