Tissue specificity of oncogenic BRAF targeted to lung and thyroid through a shared lineage factor
Summary: Cells of origin in cancer determine tumor phenotypes, but whether lineage-defining transcription factors might influence tissue specificity of tumorigenesis among organs with similar developmental traits are unknown. We demonstrate here that tumor development and progression markedly differ...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223011483 |
| _version_ | 1797774565954289664 |
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| author | Elin Schoultz Shawn Liang Therese Carlsson Stefan Filges Anders Ståhlberg Henrik Fagman Clotilde Wiel Volkan Sayin Mikael Nilsson |
| author_facet | Elin Schoultz Shawn Liang Therese Carlsson Stefan Filges Anders Ståhlberg Henrik Fagman Clotilde Wiel Volkan Sayin Mikael Nilsson |
| author_sort | Elin Schoultz |
| collection | DOAJ |
| description | Summary: Cells of origin in cancer determine tumor phenotypes, but whether lineage-defining transcription factors might influence tissue specificity of tumorigenesis among organs with similar developmental traits are unknown. We demonstrate here that tumor development and progression markedly differ in lung and thyroid targeted by Braf mutation in Nkx2.1CreERT2 mice heterozygous for Nkx2-1. In absence of tamoxifen, non-induced Nkx2.1CreERT2;BrafCA/+ mutants developed multiple full-blown lung adenocarcinomas with a latency of 1–3 months whereas thyroid tumors were rare and constrained, although minute BrafCA activation documented by variant allele sequencing was similar in both tissues. Induced oncogene activation accelerated neoplastic growth only in the lungs. By contrast, NKX2-1+ progenitor cells were equally responsive to constitutive expression of mutant Braf during lung and thyroid development. Both lung and thyroid cells transiently downregulated NKX2-1 in early tumor stages. These results indicate that BRAFV600E-induced tumorigenesis obey organ-specific traits that might be differentially modified by a shared lineage factor. |
| first_indexed | 2024-03-12T22:22:55Z |
| format | Article |
| id | doaj.art-b281298cb2e54671b8aba04ce648649c |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T22:22:55Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-b281298cb2e54671b8aba04ce648649c2023-07-23T04:55:25ZengElsevieriScience2589-00422023-07-01267107071Tissue specificity of oncogenic BRAF targeted to lung and thyroid through a shared lineage factorElin Schoultz0Shawn Liang1Therese Carlsson2Stefan Filges3Anders Ståhlberg4Henrik Fagman5Clotilde Wiel6Volkan Sayin7Mikael Nilsson8Sahlgrenska Center for Cancer Research, University of Gothenburg, Göteborg, Sweden; Department of Medical Chemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Göteborg, SwedenSahlgrenska Center for Cancer Research, University of Gothenburg, Göteborg, Sweden; Department of Medical Chemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Göteborg, SwedenSahlgrenska Center for Cancer Research, University of Gothenburg, Göteborg, Sweden; Department of Medical Chemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Göteborg, SwedenSahlgrenska Center for Cancer Research, University of Gothenburg, Göteborg, Sweden; Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Göteborg, SwedenSahlgrenska Center for Cancer Research, University of Gothenburg, Göteborg, Sweden; Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Genetics and Genomics, Göteborg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Göteborg, SwedenSahlgrenska Center for Cancer Research, University of Gothenburg, Göteborg, Sweden; Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Göteborg, SwedenSahlgrenska Center for Cancer Research, University of Gothenburg, Göteborg, Sweden; Department of Surgery, Institute of Clinical Sciences, University of Gothenburg, Göteborg, SwedenSahlgrenska Center for Cancer Research, University of Gothenburg, Göteborg, Sweden; Department of Surgery, Institute of Clinical Sciences, University of Gothenburg, Göteborg, SwedenSahlgrenska Center for Cancer Research, University of Gothenburg, Göteborg, Sweden; Department of Medical Chemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden; Corresponding authorSummary: Cells of origin in cancer determine tumor phenotypes, but whether lineage-defining transcription factors might influence tissue specificity of tumorigenesis among organs with similar developmental traits are unknown. We demonstrate here that tumor development and progression markedly differ in lung and thyroid targeted by Braf mutation in Nkx2.1CreERT2 mice heterozygous for Nkx2-1. In absence of tamoxifen, non-induced Nkx2.1CreERT2;BrafCA/+ mutants developed multiple full-blown lung adenocarcinomas with a latency of 1–3 months whereas thyroid tumors were rare and constrained, although minute BrafCA activation documented by variant allele sequencing was similar in both tissues. Induced oncogene activation accelerated neoplastic growth only in the lungs. By contrast, NKX2-1+ progenitor cells were equally responsive to constitutive expression of mutant Braf during lung and thyroid development. Both lung and thyroid cells transiently downregulated NKX2-1 in early tumor stages. These results indicate that BRAFV600E-induced tumorigenesis obey organ-specific traits that might be differentially modified by a shared lineage factor.http://www.sciencedirect.com/science/article/pii/S2589004223011483GeneticsCell biologyCancer |
| spellingShingle | Elin Schoultz Shawn Liang Therese Carlsson Stefan Filges Anders Ståhlberg Henrik Fagman Clotilde Wiel Volkan Sayin Mikael Nilsson Tissue specificity of oncogenic BRAF targeted to lung and thyroid through a shared lineage factor iScience Genetics Cell biology Cancer |
| title | Tissue specificity of oncogenic BRAF targeted to lung and thyroid through a shared lineage factor |
| title_full | Tissue specificity of oncogenic BRAF targeted to lung and thyroid through a shared lineage factor |
| title_fullStr | Tissue specificity of oncogenic BRAF targeted to lung and thyroid through a shared lineage factor |
| title_full_unstemmed | Tissue specificity of oncogenic BRAF targeted to lung and thyroid through a shared lineage factor |
| title_short | Tissue specificity of oncogenic BRAF targeted to lung and thyroid through a shared lineage factor |
| title_sort | tissue specificity of oncogenic braf targeted to lung and thyroid through a shared lineage factor |
| topic | Genetics Cell biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223011483 |
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