Immunohistochemical analysis of NOTCH1 and JAGGED1 expression in multiple myeloma and monoclonal gammopathy of undetermined significance

Škrtić, Anita; Korać, Petra; Krišto, Delfa Radić; Stojisavljević, Radmila Ajduković; Ivanković, Davor; Dominis, Mara

doi:10.1016/j.humpath.2010.05.002

Cited by 34 publications

(27 citation statements)

References 28 publications

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“…The subsequent steps were performed using the EnVision™ FLEX High pH visualisation system according to the manufacturer’s instructions (DAKO, Demark). The scoring of AMFR and NOTCH1 was performed as previous described (Tsai et al 2007; Skrtic et al 2010). …”

Section: Methodsmentioning

confidence: 99%

MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1

et al. 2014

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MicroRNAs (miRNAs) that exert function by posttranscriptional suppression have recently brought insight in our understanding of the role of non-protein-coding RNAs in carcinogenesis and metastasis. In this study, we described the function and molecular mechanism of miR-139-5p in colorectal cancer (CRC) and its potential clinical application in CRC. We found that miR-139-5p was significantly downregulated in 73.8% CRC samples compared with adjacent noncancerous tissues (NCTs), and decreased miR-139-5p was associated with poor prognosis. Functional analyses demonstrated that ectopic expression of miR-139-5p suppressed CRC cell migration and invasion in vitro and metastasis in vivo. Mechanistic investigations revealed that miR-139-5p suppress CRC cell invasion and metastasis by targeting AMFR and NOTCH1. Knockdown of the two genes phenocopied the inhibitory effect of miR-139-5p on CRC metastasis. Furthermore, the protein levels of the two genes were upregulated in CRC samples compared with NCTs, and inversely correlated with the miR-139-5p expression. Increased NOTCH1 protein expression was correlated with poor prognosis of CRC patients. Together, our data indicate that miR-139-5p is a potential tumor suppressor and prognostic factor for CRC, and targeting miR-139-5p may repress the metastasis of CRC and improve survival.Electronic supplementary materialThe online version of this article (doi:10.1007/s13238-014-0093-5) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1

et al. 2014

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“…It has been reported that Notch1 and its ligands were overexpressed in MM cell lines and human MM samples [17,18]. Some studies demonstrate that activation of Notch signaling induces growth arrest [19,20] and apoptosis [19] in multiple myeloma.…”

Section: Discussionmentioning

confidence: 99%

Notch1 overexpression promotes cell growth and tumor angiogenesis in myeloma

Guo

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Teng³

et al. 2012

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Patients with multiple myeloma (MM) have increased bone marrow angiogenesis, but the angiogenic properties of myeloma cells and the mechanism of MM-induced angiogenesis have not been completely clarified. Notch1 signal has been identified as a critical factor in the regulation of vessel formation. However, the role of Notch1 in the angiogenesis of MM is unclear. We constitutively overexpressed active Notch1 in RPMI8226 cells to explore the effect of Notch1 signaling on cell growth and tumor angiogenesis in vivo and in vitro. We found that Notch1 overexpression promoted myeloma cells growth and increased drug resistance. Moreover, vascular endothelial growth factor (VEGF) expression was increased. Finally, our in vitro results were supported by the in vivo finding in human myeloma xenograft Nonobese diabetic/severe combined immunodeficient (NOD/SCID) models. Notch1 overexpression in MM cells resulted in up-regulation of VEGF expression, promotion of tumor growth, and increased microvessel density (MVD). Our study suggests that Notch1-induced angiogenesis is partly due to activation of VEGF pathway.

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“…Non-mutated Notch1 is highly expressed in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) cells, and tumor-associated JAG1, overexpressed by bystander cells as well as by neighboring tumor cells, induces Notch1 activation and promotes tumor cell proliferation and survival (111). Similarly, in multiple myelomas, Notch1, Notch2, and JAG1 were highly expressed in primary tumor samples, and JAG1-induced Notch activation drove myeloma cell proliferation (76, 114). …”

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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Immunohistochemical analysis of NOTCH1 and JAGGED1 expression in multiple myeloma and monoclonal gammopathy of undetermined significance

Cited by 34 publications

References 28 publications

MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1

MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1

Notch1 overexpression promotes cell growth and tumor angiogenesis in myeloma

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

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