PUBLICATION
YAP Enhances Tumor Cell Dissemination by Promoting Intravascular Motility and Re-entry into Systemic Circulation
- Authors
- Benjamin, D.C., Kang, J.H., Hamza, B., King, E.M., Lamar, J.M., Manalis, S.R., Hynes, R.O.
- ID
- ZDB-PUB-200628-5
- Date
- 2020
- Source
- Cancer research 80(18): 3867-3879 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing*/metabolism
- Animals
- Cell Line, Tumor
- Cell Movement
- Mice
- Transcription Factors*/genetics
- Transcription Factors*/metabolism
- Zebrafish/metabolism
- PubMed
- 32591412 Full text @ Cancer Res.
Citation
Benjamin, D.C., Kang, J.H., Hamza, B., King, E.M., Lamar, J.M., Manalis, S.R., Hynes, R.O. (2020) YAP Enhances Tumor Cell Dissemination by Promoting Intravascular Motility and Re-entry into Systemic Circulation. Cancer research. 80(18):3867-3879.
Abstract
The oncogene YAP has been shown previously to promote tumor growth and metastasis. However, how YAP influences the behavior of tumor cells traveling within the circulatory system has not been as well explored. Given that rate-limiting steps of metastasis are known to occur while tumor cells enter, travel through, or exit circulation, we sought to study how YAP influences tumor cell behavior within the circulatory system. Intravital imaging in live zebrafish embryos revealed that YAP influenced the distribution of tumor cells within the animal following intravenous injection. Control cells became lodged in the first capillary bed encountered in the tail, whereas cells over-expressing constitutively active YAP were able to travel through this capillary plexus, re-enter systemic circulation, and seed in the brain. YAP controlled transit through these capillaries by promoting active migration within the vasculature. These results were recapitulated in a mouse model following intravenous injection, where active YAP increased the number of circulating tumor cells over time. Our results suggest a possible mechanism where tumor cells can spread to organs beyond the first capillary bed downstream from the primary tumor. These results also show that a specific gene can affect the distribution of tumor cells within an animal, thereby influencing the global pattern of metastasis in that animal.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping