Platelets reduce anoikis and promote metastasis by activating YAP1 signaling

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, Jean M. Hansen, Rajesha Rupaimoole, Kshipra M. Gharpure, Cristian Rodriguez-Aguayo, Sun Young Yim, Ju-Seog Lee, Cristina Ivan, Wei Hu, Gabriel Lopez-Berestein, Stephen T. Wong, Beth Y. Karlan, Douglas A. Levine, Jinsong Liu, Vahid Afshar-Kharghan () and Anil K. Sood ()
Additional contact information
Monika Haemmerle: The University of Texas MD Anderson Cancer Center
Morgan L. Taylor: The University of Texas MD Anderson Cancer Center
Tony Gutschner: The University of Texas MD Anderson Cancer Center
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
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
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
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

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00411-z

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