Detection of IGF2BP3, HOXB7, and NEK2 mRNA Expression in Brush Cytology Specimens as a New Diagnostic Tool in Patients with Biliary Strictures

Nischalke, Hans Dieter; Schmitz, Volker; Luda, Carolin; Aldenhoff, K.; Berger, Cordula; Feldmann, Georg; Sauerbruch, Tilman; Spengler, Ulrich; Nattermann, Jacob

doi:10.1371/journal.pone.0042141

Cited by 21 publications

(19 citation statements)

References 53 publications

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“…IGF2BP3 in particular is highly expressed in human liver tumors but not in normal liver (Figure S3A) (Wurmbach et al, 2007), and thus has been proposed as a sensitive HCC biomarker (Chen et al, 2013a; Chen et al, 2013b; Jeng et al, 2008; Nischalke et al, 2012; Wachter et al, 2012). Relatively little is known about the functional activities, biological regulation, and therapeutic relevance of these genes in cancer.…”

Section: Resultsmentioning

confidence: 99%

Lin28b Is Sufficient to Drive Liver Cancer and Necessary for Its Maintenance in Murine Models

et al. 2014

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SUMMARY Lin28a/b are RNA-binding proteins that influence stem cell maintenance, metabolism, and oncogenesis. Poorly differentiated, aggressive cancers often overexpress Lin28, but its role in tumor initiation or maintenance has not been definitively addressed. We report that LIN28B overexpression is sufficient to initiate hepatoblastoma and hepatocellular carcinoma in murine models. We also detected Lin28b overexpression in MYC-driven hepatoblastomas, and liver-specific deletion of Lin28a/b reduced tumor burden, extended latency, and prolonged survival. Both intravenous siRNA against Lin28b and conditional Lin28b deletion reduced tumor burden and prolonged survival. Igf2bp proteins are upregulated and Igf2bp3 is required in the context of LIN28B overexpression to promote growth. Thus, multiple murine models demonstrate that Lin28b is both sufficient to initiate liver cancer and necessary for its maintenance.

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Section: Resultsmentioning

confidence: 99%

Lin28b Is Sufficient to Drive Liver Cancer and Necessary for Its Maintenance in Murine Models

et al. 2014

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“…Among the top 10 genes (r 2 = 0.838) was NIMA-related kinase 2 or NEK2 . Because NEK2 is not only a well-established transcriptional target of FOXM1 in various cell lineages 46, 47 but also a driver of drug resistance in myeloma and other cancers 48–50 , we sought to confirm the co-expression of NEK2 and FOXM1 in independent datasets. This was the case in TT2 and TT3 (Supplemental Figure 6a, left ) and also in MMRF’s CoMMpass℠ study (Supplemental Figure 6a, right ), in which FOXM1 High status conferred the same kind of survival disadvantage (Supplemental Figure 6b) seen in the TT2 (Figure 1b) and TT3 (Supplemental Figure 1) cohorts.…”

Section: Resultsmentioning

confidence: 99%

FOXM1 is a therapeutic target for high-risk multiple myeloma

Yang

Sompallae

et al. 2015

Leukemia

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The transcription factor forkhead box M1 (FOXM1) is a validated oncoprotein in solid cancers, but its role in malignant plasma cell tumors such as multiple myeloma (MM) is unknown. We analyzed publicly available MM datasets and found that overexpression of FOXM1 prognosticates inferior outcome in a subset (~15%) of newly diagnosed cases, particularly patients with high-risk disease based on global gene expression changes. Follow-up studies using human myeloma cell lines (HMCLs) as the principal experimental model system demonstrated that enforced expression of FOXM1 increased growth, survival and clonogenicity of myeloma cells, whereas knockdown of FOXM1 abolished these features. In agreement with that, constitutive up-regulation of FOXM1 promoted HMCL xenografts in laboratory mice, whereas inducible knockdown of FOXM1 led to growth inhibition. Expression of cyclin dependent kinase 6 (CDK6) and NIMA-related kinase 2 (NEK2) was co-regulated with FOXM1 in both HMCLs and myeloma patient samples, suggesting interaction of these 3 genes in a genetic network that may lend itself to targeting with small-drug inhibitors for new approaches to myeloma therapy and prevention. These results establish FOXM1 as high-risk myeloma gene and provide support for the design and testing of FOXM1-targeted therapies specifically for the FOXM1High subset of myeloma.

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“…Among the top 10 genes (r 2 = 0.838) was NIMA-related kinase 2 or NEK2. Because NEK2 is not only a well-established transcriptional target of FOXM1 in various cell lineages 46,47 but also a driver of drug resistance in myeloma and other cancers 48-50 , we sought to confirm the co-expression of NEK2 and FOXM1 in independent datasets. This was the case in TT2 and TT3 (Supplemental Figure 6a, left) and also in MMRF's CoMMpass℠ study (Supplemental Figure 6a, right), in which FOXM1 High status conferred the same kind of survival disadvantage (Supplemental Figure 6b) seen in the TT2 (Figure 1b) and TT3 (Supplemental Figure 1) cohorts.…”

Section: Co-expression Of Foxm1 and Nek2 In Myelomamentioning

confidence: 99%