We are analyzing https://link.springer.com/article/10.1186/s13045-018-0615-3.

Title:
Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential | Journal of Hematology & Oncology
Description:
Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow. In the vast majority of patients, this results in osteolytic bone disease, which is associated with bone pain and pathological fractures and was reported to facilitate disease progression. More recently, cumulative evidence also indicates the importance of intrinsic Wnt signaling in the survival of multiple myeloma cells. However, Wnt pathway-activating gene mutations could not be identified. The search for factors or processes responsible for Wnt pathway activation currently focuses on aberrant ligand levels in the bone marrow microenvironment, increased expression of Wnt transcriptional co-factors and associated micro-RNAs, and disturbed epigenetics and post-translational modification processes. Furthermore, Wnt pathway activation is associated with acquired cell adhesion-mediated resistance of multiple myeloma cells to conventional drug therapies, including doxorubicin and lenalidomide. In this review, we present an overview of the relevance of Wnt signaling in multiple myeloma and highlight the Wnt pathway as a potential therapeutic target for this disease.
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Keywords {🔍}

wnt, pubmed, signaling, cells, google, scholar, article, bone, cas, cell, pathway, myeloma, multiple, canonical, βcatenin, central, disease, activation, cancer, active, levels, growth, target, tumor, including, reported, treatment, expression, role, patients, osteoblasts, factors, hmcls, fzd, dkk, study, development, genes, drug, results, gene, increased, ligands, wnta, complex, showed, resistance, stem, survival, result,

Topics {✒️}

β-catenin-lef/tcf mediated transcription β-catenin-lef/tcf antagonists pkf115-584 oncogenic wnt/beta-catenin/bcl9 pathway high-throughput elisa-based screen β-catenin-lef/tcf antagonists nuclear beta-catenin-tcf complex beta-catenin/tcf transcriptional complex tcf/lef-family transcription factors wnt/β-catenin-mediated transcription intrinsic wnt/β-catenin pathway downstream wnt/β-catenin signaling wnt/beta-catenin signaling pathway nod/scid/gamma mice transplanted canonical wnt/β-catenin pathway r-spondin/lgr5/rnf43 module wnt/β-catenin transcriptional activity antibody-based inhibitor opm-54f28 aberrant r-spondin-lgr signaling tcf/lef-mediated transcription wnt3/rhoa/rock signaling pathway transcriptionally active β-catenin beta-catenin/tcf pathway inducing nfat-mediated transcription prior skeletal-related events membrane-bound o-acetyltransferase tgf-beta signalling pathways constitutively active β-catenin complex marks β-catenin hijacking osteoblast-derived r-spondins beta-catenin destruction complex continuously synthesized β-catenin nfat-mediated transcriptional programs nuclear arm/beta-catenin lef/tcf transcription factors rank/rankl/opg signaling axis e3 ligase β-trcp article download pdf β-catenin destruction complex wnt-fzd-lrp-dvl axis adhesion-mediated drug resistance targeted therapy wnt/β-catenin agonists lef/tcf family members wnt/beta-catenin signaling beta-catenin inhibitor bc2059 de vries-smits lm beta-catenin/wnt pathways ingenious feedback/feedforward loop inhibits wnt-driven phosphorylation β-catenin inhibitor bc2059

Questions {❓}

Can we safely target the WNT pathway?
Wnt signaling in cervical cancer?

Schema {🗺️}

WebPage:
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         headline:Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential
         description:Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow. In the vast majority of patients, this results in osteolytic bone disease, which is associated with bone pain and pathological fractures and was reported to facilitate disease progression. More recently, cumulative evidence also indicates the importance of intrinsic Wnt signaling in the survival of multiple myeloma cells. However, Wnt pathway-activating gene mutations could not be identified. The search for factors or processes responsible for Wnt pathway activation currently focuses on aberrant ligand levels in the bone marrow microenvironment, increased expression of Wnt transcriptional co-factors and associated micro-RNAs, and disturbed epigenetics and post-translational modification processes. Furthermore, Wnt pathway activation is associated with acquired cell adhesion-mediated resistance of multiple myeloma cells to conventional drug therapies, including doxorubicin and lenalidomide. In this review, we present an overview of the relevance of Wnt signaling in multiple myeloma and highlight the Wnt pathway as a potential therapeutic target for this disease.
         datePublished:2018-05-18T00:00:00Z
         dateModified:2018-05-18T00:00:00Z
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            Hematology
            Cancer Research
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      headline:Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential
      description:Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow. In the vast majority of patients, this results in osteolytic bone disease, which is associated with bone pain and pathological fractures and was reported to facilitate disease progression. More recently, cumulative evidence also indicates the importance of intrinsic Wnt signaling in the survival of multiple myeloma cells. However, Wnt pathway-activating gene mutations could not be identified. The search for factors or processes responsible for Wnt pathway activation currently focuses on aberrant ligand levels in the bone marrow microenvironment, increased expression of Wnt transcriptional co-factors and associated micro-RNAs, and disturbed epigenetics and post-translational modification processes. Furthermore, Wnt pathway activation is associated with acquired cell adhesion-mediated resistance of multiple myeloma cells to conventional drug therapies, including doxorubicin and lenalidomide. In this review, we present an overview of the relevance of Wnt signaling in multiple myeloma and highlight the Wnt pathway as a potential therapeutic target for this disease.
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      dateModified:2018-05-18T00:00:00Z
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         Wnt signaling
         β-catenin
         Osteolytic bone disease
         Drug resistance
         Targeted therapy
         Oncology
         Hematology
         Cancer Research
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      affiliation:
            name:Philips Research
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      affiliation:
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            address:
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      name:Department of Hematology, University Medical Center Utrecht, Utrecht, the Netherlands
      name:Molecular Diagnostics, Philips Research, Eindhoven, the Netherlands
      name:Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands

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