Active receptor tyrosine kinases, but not Brachyury, are sufficient to trigger chordoma in zebrafish Article Swipe
Gianluca D‘Agati
,
Elena M. Cabello
,
Karl Frontzek
,
Elisabeth J. Rushing
,
Robin W. Klemm
,
Mark D. Robinson
,
Richard M. White
,
Christian Mosimann
,
Alexa Burger
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1242/dmm.039545
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1242/dmm.039545
The aberrant activation of developmental processes triggers diverse cancer types. Chordoma is a rare, aggressive tumor arising from transformed notochord remnants. Several potentially oncogenic factors have been found to be deregulated in chordoma, yet causation remains uncertain. In particular, sustained expression of TBXT – encoding the notochord regulator protein brachyury – is hypothesized as a key driver of chordoma, yet experimental evidence is absent. Here, we employ a zebrafish chordoma model to identify the notochord-transforming potential of implicated genes in vivo. We find that Brachyury, including a form with augmented transcriptional activity, is insufficient to initiate notochord hyperplasia. In contrast, the chordoma-implicated receptor tyrosine kinases (RTKs) EGFR and Kdr/VEGFR2 are sufficient to transform notochord cells. Aberrant activation of RTK/Ras signaling attenuates processes required for notochord differentiation, including the unfolded protein response and endoplasmic reticulum stress pathways. Our results provide the first in vivo evidence against a tumor-initiating potential of Brachyury in the notochord, and imply activated RTK signaling as a possible initiating event in chordoma. Furthermore, our work points at modulating endoplasmic reticulum and protein stress pathways as possible therapeutic avenues against chordoma.
Related Topics
Concepts
Brachyury
Zebrafish
Receptor tyrosine kinase
Receptor Protein-Tyrosine Kinases
Biology
Tyrosine kinase
Chordoma
Kinase
Cell biology
Receptor
Cancer research
Signal transduction
Medicine
Genetics
Mesoderm
Gene
Pathology
Embryonic stem cell
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1242/dmm.039545
- https://dmm.biologists.org/content/dmm/12/7/dmm039545.full.pdf
- OA Status
- gold
- Cited By
- 16
- References
- 109
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2952808666
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2952808666Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1242/dmm.039545Digital Object Identifier
- Title
-
Active receptor tyrosine kinases, but not Brachyury, are sufficient to trigger chordoma in zebrafishWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-06-20Full publication date if available
- Authors
-
Gianluca D‘Agati, Elena M. Cabello, Karl Frontzek, Elisabeth J. Rushing, Robin W. Klemm, Mark D. Robinson, Richard M. White, Christian Mosimann, Alexa BurgerList of authors in order
- Landing page
-
https://doi.org/10.1242/dmm.039545Publisher landing page
- PDF URL
-
https://dmm.biologists.org/content/dmm/12/7/dmm039545.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://dmm.biologists.org/content/dmm/12/7/dmm039545.full.pdfDirect OA link when available
- Concepts
-
Brachyury, Zebrafish, Receptor tyrosine kinase, Receptor Protein-Tyrosine Kinases, Biology, Tyrosine kinase, Chordoma, Kinase, Cell biology, Receptor, Cancer research, Signal transduction, Medicine, Genetics, Mesoderm, Gene, Pathology, Embryonic stem cellTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
16Total citation count in OpenAlex
- Citations by year (recent)
-
2024: 1, 2023: 4, 2022: 5, 2021: 3, 2020: 3Per-year citation counts (last 5 years)
- References (count)
-
109Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.cells. | 115 |
| abstract_inverted_index.driver | 57 |
| abstract_inverted_index.employ | 67 |
| abstract_inverted_index.points | 169 |
| abstract_inverted_index.stress | 135, 176 |
| abstract_inverted_index.types. | 10 |
| abstract_inverted_index.RTK/Ras | 119 |
| abstract_inverted_index.Several | 22 |
| abstract_inverted_index.absent. | 64 |
| abstract_inverted_index.against | 145, 182 |
| abstract_inverted_index.arising | 17 |
| abstract_inverted_index.avenues | 181 |
| abstract_inverted_index.diverse | 8 |
| abstract_inverted_index.factors | 25 |
| abstract_inverted_index.kinases | 105 |
| abstract_inverted_index.protein | 49, 130, 175 |
| abstract_inverted_index.provide | 139 |
| abstract_inverted_index.remains | 36 |
| abstract_inverted_index.results | 138 |
| abstract_inverted_index.ABSTRACT | 0 |
| abstract_inverted_index.Aberrant | 116 |
| abstract_inverted_index.Chordoma | 11 |
| abstract_inverted_index.aberrant | 2 |
| abstract_inverted_index.chordoma | 70 |
| abstract_inverted_index.encoding | 45 |
| abstract_inverted_index.evidence | 62, 144 |
| abstract_inverted_index.identify | 73 |
| abstract_inverted_index.initiate | 96 |
| abstract_inverted_index.pathways | 177 |
| abstract_inverted_index.possible | 161, 179 |
| abstract_inverted_index.receptor | 103 |
| abstract_inverted_index.required | 123 |
| abstract_inverted_index.response | 131 |
| abstract_inverted_index.triggers | 7 |
| abstract_inverted_index.tyrosine | 104 |
| abstract_inverted_index.unfolded | 129 |
| abstract_inverted_index.Brachyury | 150 |
| abstract_inverted_index.activated | 156 |
| abstract_inverted_index.activity, | 92 |
| abstract_inverted_index.augmented | 90 |
| abstract_inverted_index.brachyury | 50 |
| abstract_inverted_index.causation | 35 |
| abstract_inverted_index.chordoma, | 33, 59 |
| abstract_inverted_index.chordoma. | 165, 183 |
| abstract_inverted_index.contrast, | 100 |
| abstract_inverted_index.including | 86, 127 |
| abstract_inverted_index.notochord | 20, 47, 97, 114, 125 |
| abstract_inverted_index.oncogenic | 24 |
| abstract_inverted_index.pathways. | 136 |
| abstract_inverted_index.potential | 76, 148 |
| abstract_inverted_index.processes | 6, 122 |
| abstract_inverted_index.regulator | 48 |
| abstract_inverted_index.remnants. | 21 |
| abstract_inverted_index.reticulum | 134, 173 |
| abstract_inverted_index.signaling | 120, 158 |
| abstract_inverted_index.sustained | 40 |
| abstract_inverted_index.transform | 113 |
| abstract_inverted_index.zebrafish | 69 |
| abstract_inverted_index.Brachyury, | 85 |
| abstract_inverted_index.Kdr/VEGFR2 | 109 |
| abstract_inverted_index.activation | 3, 117 |
| abstract_inverted_index.aggressive | 15 |
| abstract_inverted_index.attenuates | 121 |
| abstract_inverted_index.expression | 41 |
| abstract_inverted_index.implicated | 78 |
| abstract_inverted_index.initiating | 162 |
| abstract_inverted_index.modulating | 171 |
| abstract_inverted_index.notochord, | 153 |
| abstract_inverted_index.sufficient | 111 |
| abstract_inverted_index.uncertain. | 37 |
| abstract_inverted_index.deregulated | 31 |
| abstract_inverted_index.endoplasmic | 133, 172 |
| abstract_inverted_index.particular, | 39 |
| abstract_inverted_index.potentially | 23 |
| abstract_inverted_index.therapeutic | 180 |
| abstract_inverted_index.transformed | 19 |
| abstract_inverted_index.Furthermore, | 166 |
| abstract_inverted_index.experimental | 61 |
| abstract_inverted_index.hyperplasia. | 98 |
| abstract_inverted_index.hypothesized | 53 |
| abstract_inverted_index.insufficient | 94 |
| abstract_inverted_index.developmental | 5 |
| abstract_inverted_index.transcriptional | 91 |
| abstract_inverted_index.differentiation, | 126 |
| abstract_inverted_index.tumor-initiating | 147 |
| abstract_inverted_index.chordoma-implicated | 102 |
| abstract_inverted_index.notochord-transforming | 75 |
| cited_by_percentile_year.max | 98 |
| cited_by_percentile_year.min | 90 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 9 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.44999998807907104 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.86076184 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |