11q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in Neuroblastoma
Summary: High-risk neuroblastomas typically display an undifferentiated or poorly differentiated morphology. It is therefore vital to understand molecular mechanisms that block the differentiation process. We identify an important role for oncogenic ALK-ERK1/2-SP1 signaling in the maintenance of und...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720311608 |
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doaj-01191b05e5974287a9be5d2989de4d0a |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Joachim Tetteh Siaw Niloufar Javanmardi Jimmy Van den Eynden Dan Emil Lind Susanne Fransson Angela Martinez-Monleon Anna Djos Rose-Marie Sjöberg Malin Östensson Helena Carén Gunhild Trøen Klaus Beiske Ana P. Berbegall Rosa Noguera Wei-Yun Lai Per Kogner Ruth H. Palmer Bengt Hallberg Tommy Martinsson |
| spellingShingle |
Joachim Tetteh Siaw Niloufar Javanmardi Jimmy Van den Eynden Dan Emil Lind Susanne Fransson Angela Martinez-Monleon Anna Djos Rose-Marie Sjöberg Malin Östensson Helena Carén Gunhild Trøen Klaus Beiske Ana P. Berbegall Rosa Noguera Wei-Yun Lai Per Kogner Ruth H. Palmer Bengt Hallberg Tommy Martinsson 11q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in Neuroblastoma Cell Reports ALK neuroblastoma DLG2 tumor suppressor retinoic acid ERK |
| author_facet |
Joachim Tetteh Siaw Niloufar Javanmardi Jimmy Van den Eynden Dan Emil Lind Susanne Fransson Angela Martinez-Monleon Anna Djos Rose-Marie Sjöberg Malin Östensson Helena Carén Gunhild Trøen Klaus Beiske Ana P. Berbegall Rosa Noguera Wei-Yun Lai Per Kogner Ruth H. Palmer Bengt Hallberg Tommy Martinsson |
| author_sort |
Joachim Tetteh Siaw |
| title |
11q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in Neuroblastoma |
| title_short |
11q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in Neuroblastoma |
| title_full |
11q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in Neuroblastoma |
| title_fullStr |
11q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in Neuroblastoma |
| title_full_unstemmed |
11q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in Neuroblastoma |
| title_sort |
11q deletion or alk activity curbs dlg2 expression to maintain an undifferentiated state in neuroblastoma |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2020-09-01 |
| description |
Summary: High-risk neuroblastomas typically display an undifferentiated or poorly differentiated morphology. It is therefore vital to understand molecular mechanisms that block the differentiation process. We identify an important role for oncogenic ALK-ERK1/2-SP1 signaling in the maintenance of undifferentiated neural crest-derived progenitors through the repression of DLG2, a candidate tumor suppressor gene in neuroblastoma. DLG2 is expressed in the murine “bridge signature” that represents the transcriptional transition state when neural crest cells or Schwann cell precursors differentiate to chromaffin cells of the adrenal gland. We show that the restoration of DLG2 expression spontaneously drives neuroblastoma cell differentiation, highlighting the importance of DLG2 in this process. These findings are supported by genetic analyses of high-risk 11q deletion neuroblastomas, which identified genetic lesions in the DLG2 gene. Our data also suggest that further exploration of other bridge genes may help elucidate the mechanisms underlying the differentiation of NC-derived progenitors and their contribution to neuroblastomas. |
| topic |
ALK neuroblastoma DLG2 tumor suppressor retinoic acid ERK |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124720311608 |
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| _version_ |
1725099107054256128 |
| spelling |
doaj-01191b05e5974287a9be5d2989de4d0a2020-11-25T01:29:00ZengElsevierCell Reports2211-12472020-09-01321210817111q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in NeuroblastomaJoachim Tetteh Siaw0Niloufar Javanmardi1Jimmy Van den Eynden2Dan Emil Lind3Susanne Fransson4Angela Martinez-Monleon5Anna Djos6Rose-Marie Sjöberg7Malin Östensson8Helena Carén9Gunhild Trøen10Klaus Beiske11Ana P. Berbegall12Rosa Noguera13Wei-Yun Lai14Per Kogner15Ruth H. Palmer16Bengt Hallberg17Tommy Martinsson18Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, SwedenDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530 Gothenburg, SwedenDepartment of Human Structure and Repair, Anatomy and Embryology Unit, Ghent University, 9000 Ghent, BelgiumDepartment of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, SwedenDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530 Gothenburg, SwedenDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530 Gothenburg, SwedenDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530 Gothenburg, SwedenDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530 Gothenburg, SwedenBioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, SwedenSahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenInstitute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Pathology, Oslo University Hospital, Oslo, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Pathology, Oslo University Hospital, Oslo, NorwayDepartment of Pathology, Medical School, University of Valencia/INCLIVA, Valencia/CIBER of Cancer, Madrid, SpainDepartment of Pathology, Medical School, University of Valencia/INCLIVA, Valencia/CIBER of Cancer, Madrid, SpainDepartment of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, SwedenChildhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, SwedenDepartment of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden; Corresponding authorDepartment of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden; Corresponding authorDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530 Gothenburg, Sweden; Corresponding authorSummary: High-risk neuroblastomas typically display an undifferentiated or poorly differentiated morphology. It is therefore vital to understand molecular mechanisms that block the differentiation process. We identify an important role for oncogenic ALK-ERK1/2-SP1 signaling in the maintenance of undifferentiated neural crest-derived progenitors through the repression of DLG2, a candidate tumor suppressor gene in neuroblastoma. DLG2 is expressed in the murine “bridge signature” that represents the transcriptional transition state when neural crest cells or Schwann cell precursors differentiate to chromaffin cells of the adrenal gland. We show that the restoration of DLG2 expression spontaneously drives neuroblastoma cell differentiation, highlighting the importance of DLG2 in this process. These findings are supported by genetic analyses of high-risk 11q deletion neuroblastomas, which identified genetic lesions in the DLG2 gene. Our data also suggest that further exploration of other bridge genes may help elucidate the mechanisms underlying the differentiation of NC-derived progenitors and their contribution to neuroblastomas.http://www.sciencedirect.com/science/article/pii/S2211124720311608ALKneuroblastomaDLG2tumor suppressorretinoic acidERK |