Identification of a neural development gene expression signature in colon cancer stem cells reveals a role for EGR2 in tumorigenesis
Summary: Recent evidence demonstrates that colon cancer stem cells (CSCs) can generate neurons that synapse with tumor innervating fibers required for tumorigenesis and disease progression. Greater understanding of the mechanisms that regulate CSC driven tumor neurogenesis may therefore lead to more...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222007696 |
| _version_ | 1818552432955752448 |
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| author | Joseph L. Regan Dirk Schumacher Stephanie Staudte Andreas Steffen Ralf Lesche Joern Toedling Thibaud Jourdan Johannes Haybaeck Nicole Golob-Schwarzl Dominik Mumberg David Henderson Balázs Győrffy Christian R.A. Regenbrecht Ulrich Keilholz Reinhold Schäfer Martin Lange |
| author_facet | Joseph L. Regan Dirk Schumacher Stephanie Staudte Andreas Steffen Ralf Lesche Joern Toedling Thibaud Jourdan Johannes Haybaeck Nicole Golob-Schwarzl Dominik Mumberg David Henderson Balázs Győrffy Christian R.A. Regenbrecht Ulrich Keilholz Reinhold Schäfer Martin Lange |
| author_sort | Joseph L. Regan |
| collection | DOAJ |
| description | Summary: Recent evidence demonstrates that colon cancer stem cells (CSCs) can generate neurons that synapse with tumor innervating fibers required for tumorigenesis and disease progression. Greater understanding of the mechanisms that regulate CSC driven tumor neurogenesis may therefore lead to more effective treatments. RNA-sequencing analyses of ALDHPositive CSCs from colon cancer patient-derived organoids (PDOs) and xenografts (PDXs) showed CSCs to be enriched for neural development genes. Functional analyses of genes differentially expressed in CSCs from PDO and PDX models demonstrated the neural crest stem cell (NCSC) regulator EGR2 to be required for tumor growth and to control expression of homebox superfamily embryonic master transcriptional regulator HOX genes and the neural stem cell and master cell fate regulator SOX2. These data support CSCs as the source of tumor neurogenesis and suggest that targeting EGR2 may provide a therapeutic differentiation strategy to eliminate CSCs and block nervous system driven disease progression. |
| first_indexed | 2024-12-12T09:13:07Z |
| format | Article |
| id | doaj.art-10e2b87481c14205bdb2aca8b985954b |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-12T09:13:07Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-10e2b87481c14205bdb2aca8b985954b2022-12-22T00:29:28ZengElsevieriScience2589-00422022-07-01257104498Identification of a neural development gene expression signature in colon cancer stem cells reveals a role for EGR2 in tumorigenesisJoseph L. Regan0Dirk Schumacher1Stephanie Staudte2Andreas Steffen3Ralf Lesche4Joern Toedling5Thibaud Jourdan6Johannes Haybaeck7Nicole Golob-Schwarzl8Dominik Mumberg9David Henderson10Balázs Győrffy11Christian R.A. Regenbrecht12Ulrich Keilholz13Reinhold Schäfer14Martin Lange15Bayer AG, Research and Development, Pharmaceuticals, 13342 Berlin, Germany; Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany; Corresponding authorLaboratory of Molecular Tumor Pathology, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany; German Cancer Consortium (DKTK), DKFZ, 69120 Heidelberg, GermanyBayer AG, Research and Development, Pharmaceuticals, 13342 Berlin, Germany; German Cancer Consortium (DKTK), DKFZ, 69120 Heidelberg, Germany; Department of Radiation Oncology and Radiotherapy, Charité - Universitätsmedizin Berlin, 10117 Berlin, GermanyBayer AG, Research and Development, Pharmaceuticals, 13342 Berlin, GermanyBayer AG, Research and Development, Pharmaceuticals, 13342 Berlin, Germany; Nuvisan ICB GmbH, 13353 Berlin, GermanyBayer AG, Research and Development, Pharmaceuticals, 13342 Berlin, Germany; Nuvisan ICB GmbH, 13353 Berlin, GermanyBayer AG, Research and Development, Pharmaceuticals, 13342 Berlin, GermanyInstitute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, 6020 Innsbruck, Austria; Diagnostic and Research Center for Molecular Biomedicine, Institute of Pathology, Medical University of Graz, 8036 Graz, AustriaInstitute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, 6020 Innsbruck, Austria; Department of Dermatology and Venereology, Medical University of Graz, 8036 Graz, AustriaBayer AG, Research and Development, Pharmaceuticals, 13342 Berlin, GermanyBayer AG, Research and Development, Pharmaceuticals, 13342 Berlin, Germany; Bayer AG, Business Development and Licensing and Open Innovation, Pharmaceuticals, 13342 Berlin, GermanyDepartment of Bioinformatics, Semmelweis University, 1094 Budapest, Hungary; TTK Cancer Biomarker Research Group, Institute of Enzymology, 1117 Budapest, HungaryLaboratory of Molecular Tumor Pathology, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany; CELLphenomics GmbH, 13125 Berlin, Germany; Institute of Pathology, University Medical Center Göttingen, 37075 Göttingen, GermanyCharité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, 10117 Berlin, GermanyCharité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany; Laboratory of Molecular Tumor Pathology, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany; German Cancer Consortium (DKTK), DKFZ, 69120 Heidelberg, GermanyBayer AG, Research and Development, Pharmaceuticals, 13342 Berlin, Germany; Nuvisan ICB GmbH, 13353 Berlin, GermanySummary: Recent evidence demonstrates that colon cancer stem cells (CSCs) can generate neurons that synapse with tumor innervating fibers required for tumorigenesis and disease progression. Greater understanding of the mechanisms that regulate CSC driven tumor neurogenesis may therefore lead to more effective treatments. RNA-sequencing analyses of ALDHPositive CSCs from colon cancer patient-derived organoids (PDOs) and xenografts (PDXs) showed CSCs to be enriched for neural development genes. Functional analyses of genes differentially expressed in CSCs from PDO and PDX models demonstrated the neural crest stem cell (NCSC) regulator EGR2 to be required for tumor growth and to control expression of homebox superfamily embryonic master transcriptional regulator HOX genes and the neural stem cell and master cell fate regulator SOX2. These data support CSCs as the source of tumor neurogenesis and suggest that targeting EGR2 may provide a therapeutic differentiation strategy to eliminate CSCs and block nervous system driven disease progression.http://www.sciencedirect.com/science/article/pii/S2589004222007696Stem cells researchCancerTranscriptomics |
| spellingShingle | Joseph L. Regan Dirk Schumacher Stephanie Staudte Andreas Steffen Ralf Lesche Joern Toedling Thibaud Jourdan Johannes Haybaeck Nicole Golob-Schwarzl Dominik Mumberg David Henderson Balázs Győrffy Christian R.A. Regenbrecht Ulrich Keilholz Reinhold Schäfer Martin Lange Identification of a neural development gene expression signature in colon cancer stem cells reveals a role for EGR2 in tumorigenesis iScience Stem cells research Cancer Transcriptomics |
| title | Identification of a neural development gene expression signature in colon cancer stem cells reveals a role for EGR2 in tumorigenesis |
| title_full | Identification of a neural development gene expression signature in colon cancer stem cells reveals a role for EGR2 in tumorigenesis |
| title_fullStr | Identification of a neural development gene expression signature in colon cancer stem cells reveals a role for EGR2 in tumorigenesis |
| title_full_unstemmed | Identification of a neural development gene expression signature in colon cancer stem cells reveals a role for EGR2 in tumorigenesis |
| title_short | Identification of a neural development gene expression signature in colon cancer stem cells reveals a role for EGR2 in tumorigenesis |
| title_sort | identification of a neural development gene expression signature in colon cancer stem cells reveals a role for egr2 in tumorigenesis |
| topic | Stem cells research Cancer Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222007696 |
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