Author
Listed:
- Monika Haemmerle
(The University of Texas MD Anderson Cancer Center
Martin-Luther-University Halle-Wittenberg)
- Morgan L. Taylor
(The University of Texas MD Anderson Cancer Center)
- Tony Gutschner
(The University of Texas MD Anderson Cancer Center
Martin-Luther-University Halle-Wittenberg, Halle (Saale))
- Sunila Pradeep
(The University of Texas MD Anderson Cancer Center)
- Min Soon Cho
(The University of Texas MD Anderson Cancer Center)
- Jianting Sheng
(Houston Methodist Research Institute, Houston Methodist Hospital)
- Yasmin M. Lyons
(The University of Texas MD Anderson Cancer Center)
- Archana S. Nagaraja
(The University of Texas MD Anderson Cancer Center)
- Robert L. Dood
(The University of Texas MD Anderson Cancer Center)
- Yunfei Wen
(The University of Texas MD Anderson Cancer Center)
- Lingegowda S. Mangala
(The University of Texas MD Anderson Cancer Center
The University of Texas MD Anderson Cancer Center)
- Jean M. Hansen
(The University of Texas MD Anderson Cancer Center)
- Rajesha Rupaimoole
(The University of Texas MD Anderson Cancer Center)
- Kshipra M. Gharpure
(The University of Texas MD Anderson Cancer Center)
- Cristian Rodriguez-Aguayo
(The University of Texas MD Anderson Cancer Center
The University of Texas MD Anderson Cancer Center)
- Sun Young Yim
(The University of Texas MD Anderson Cancer Center)
- Ju-Seog Lee
(The University of Texas MD Anderson Cancer Center)
- Cristina Ivan
(The University of Texas MD Anderson Cancer Center)
- Wei Hu
(The University of Texas MD Anderson Cancer Center)
- Gabriel Lopez-Berestein
(The University of Texas MD Anderson Cancer Center
The University of Texas MD Anderson Cancer Center)
- Stephen T. Wong
(Houston Methodist Research Institute, Houston Methodist Hospital)
- Beth Y. Karlan
(Cedars-Sinai Medical Center, Geffen School of Medicine at UCLA)
- Douglas A. Levine
(Laura and Isaac Perlmutter Cancer Centre, NYU Langone Medical Center)
- Jinsong Liu
(The University of Texas MD Anderson Cancer Center)
- Vahid Afshar-Kharghan
(The University of Texas MD Anderson Cancer Center)
- Anil K. Sood
(The University of Texas MD Anderson Cancer Center
The University of Texas MD Anderson Cancer Center
The University of Texas MD Anderson Cancer Center)
Abstract
Thrombocytosis is present in more than 30% of patients with solid malignancies and correlates with worsened patient survival. Tumor cell interaction with various cellular components of the tumor microenvironment including platelets is crucial for tumor growth and metastasis. Although it is known that platelets can infiltrate into tumor tissue, secrete pro-angiogenic and pro-tumorigenic factors and thereby increase tumor growth, the precise molecular interactions between platelets and metastatic cancer cells are not well understood. Here we demonstrate that platelets induce resistance to anoikis in vitro and are critical for metastasis in vivo. We further show that platelets activate RhoA-MYPT1-PP1-mediated YAP1 dephosphorylation and promote its nuclear translocation which induces a pro-survival gene expression signature and inhibits apoptosis. Reduction of YAP1 in cancer cells in vivo protects against thrombocytosis-induced increase in metastasis. Collectively, our results indicate that cancer cells depend on platelets to avoid anoikis and succeed in the metastatic process.
Suggested Citation
Monika Haemmerle & Morgan L. Taylor & Tony Gutschner & Sunila Pradeep & Min Soon Cho & Jianting Sheng & Yasmin M. Lyons & Archana S. Nagaraja & Robert L. Dood & Yunfei Wen & Lingegowda S. Mangala & Je, 2017.
"Platelets reduce anoikis and promote metastasis by activating YAP1 signaling,"
Nature Communications, Nature, vol. 8(1), pages 1-15, December.
Handle:
RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00411-z
DOI: 10.1038/s41467-017-00411-z
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