Up-regulated expression of Notch1 and Jagged1 in human colon adenocarcinoma

Gao, Juan; Liu, J.; Fan, Daiming; Xu, Hualin; Xiong, Yimin; Wang, Yuhang; Xu, Weitian; C, Yi; Guo, Zheng

doi:10.1016/j.patbio.2010.11.001

Cited by 20 publications

(14 citation statements)

References 32 publications

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“…However, it was demonstrated that in spheroids, all genes in Notch signaling are significantly upregulated, particularly Jagged1 , DLL3 and Notch1 . High Jagged1 expression has been demonstrated to predict a worse outcome in breast cancer (35,36), renal cell carcinoma (37) and colon adenocarcinoma (38). It has also been reported that high Jagged1 expression is associated with prostate cancer recurrence (39).…”

Section: Discussionmentioning

confidence: 99%

Expression profiling of stem cell signaling alters with spheroid formation in CD133high/CD44high prostate cancer stem cells

et al. 2014

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Cancer stem cells (CSC) isolated from multiple tumor types differentiate in vivo and in vitro when cultured in serum; however, the factors responsible for their differentiation have not yet been identified. The first aim of the present study was to identify CD133high/CD44high DU145 prostate CSCs and compare their profiles with non-CSCs as bulk counterparts of the population. Subsequently, the two populations continued to be three-dimensional multicellular spheroids. Differentiation was then investigated with stem cell-related genomic characteristics. Polymerase chain reaction array analyses of cell cycle regulation, embryonic and mesenchymal cell lineage-related markers, and telomerase reverse transcriptase (TERT) and Notch signaling were performed. Immunohistochemistry of CD117, Notch1, Jagged1, Delta1, Sox2, c-Myc, Oct4, KLF4, CD90 and SSEA1 were determined in CSC and non-CSC monolayer and spheroid subcultures. Significant gene alterations were observed in the CD133high/CD44high population when cultured as a monolayer and continued as spheroid. In this group, marked gene upregulation was determined in collagen type 9 α1, Islet1 and cyclin D2. Jagged1, Delta-like 3 and Notch1 were respectively upregulated genes in the Notch signaling pathway. According to immunoreactivity, the staining density of Jagged1, Sox2, Oct4 and Klf-4 increased significantly in CSC spheroids. Isolated CSCs alter their cellular characterization over the course of time and exhibit a differentiation profile while maintaining their former surface antigens at a level of transcription or translation. The current study suggested that this differentiation process may be a mechanism responsible for the malignant process and tumor growth.

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Section: Discussionmentioning

confidence: 99%

Expression profiling of stem cell signaling alters with spheroid formation in CD133high/CD44high prostate cancer stem cells

et al. 2014

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“…The cause of Notch overactivation in colon cancer appears to be ligand-dependent and to correlate with elevated JAG1 expression levels (73, 94). Accordingly, JAG1 knockdown leads to reduced Notch signaling activity that is accompanied by cell growth inhibition, cell cycle arrest, migration, and invasion inhibition, as well as tumor growth suppression (73).…”

Section: Jag1 In Individual Cancer Typesmentioning

confidence: 99%

The Notch ligand Jagged1 as a target for anti-tumor therapy

et al. 2014

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The Notch pathway is increasingly attracting attention as a source of therapeutic targets for cancer. Ligand-induced Notch signaling has been implicated in various aspects of cancer biology; as a consequence, pan-Notch inhibitors and therapeutic antibodies targeting one or more of the Notch receptors have been investigated for cancer therapy. Alternatively, Notch ligands provide attractive options for therapy in cancer treatment due to their more restricted expression and better-defined functions, as well as their low rate of mutations in cancer. One of the Notch ligands, Jagged1 (JAG1), is overexpressed in many cancer types, and plays an important role in several aspects of tumor biology. In fact, JAG1-stimulated Notch activation is directly implicated in tumor growth through maintaining cancer stem cell populations, promoting cell survival, inhibiting apoptosis, and driving cell proliferation and metastasis. In addition, JAG1 can indirectly affect cancer by influencing tumor microenvironment components such as tumor vasculature and immune cell infiltration. This article gives an overview of JAG1 and its role in tumor biology, and its potential as a therapeutic target.

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“…Recent studies have revealed the deregulation of expression and function of Notch receptors and ligands in a series of malignant tumors. The expression of Notch1 and Jagged1 are upregulated in human colon adenocarcinoma (3). Notch1, Notch2, and hairy and enhancer of split 1 (HES1) show high expression in biliary tract cancer (4).…”

Section: Introductionmentioning

confidence: 99%