YAP Enhances Tumor Cell Dissemination by Promoting Intravascular Motility and Reentry into Systemic Circulation.
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
15 09 2020
15 09 2020
Historique:
received:
27
01
2020
revised:
28
04
2020
accepted:
23
06
2020
pubmed:
28
6
2020
medline:
13
1
2021
entrez:
28
6
2020
Statut:
ppublish
Résumé
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 overexpressing constitutively active YAP were able to travel through this capillary plexus, reenter systemic circulation, and seed in the brain. YAP controlled transit through these capillaries by promoting active migration within the vasculature. These results were corroborated 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 whereby 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. SIGNIFICANCE: These findings demonstrate that YAP endows tumor cells with the ability to move through capillaries, allowing them to return to and persist in circulation, thereby increasing their metastatic spread.
Identifiants
pubmed: 32591412
pii: 0008-5472.CAN-20-0212
doi: 10.1158/0008-5472.CAN-20-0212
pmc: PMC7501173
mid: NIHMS1608504
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Comment
Langues
eng
Sous-ensembles de citation
IM
Pagination
3867-3879Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM007287
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014051
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA163109
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA217377
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA184956
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentOn
Informations de copyright
©2020 American Association for Cancer Research.
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