Platelets reduce anoikis and promote metastasis by activating YAP1 signaling

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 tha...

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Published in:Nature communications Vol. 8; no. 1; pp. 310 - 15
Main Authors: Haemmerle, Monika, Taylor, Morgan L., Gutschner, Tony, Pradeep, Sunila, Cho, Min Soon, Sheng, Jianting, Lyons, Yasmin M., Nagaraja, Archana S., Dood, Robert L., Wen, Yunfei, Mangala, Lingegowda S., Hansen, Jean M., Rupaimoole, Rajesha, Gharpure, Kshipra M., Rodriguez-Aguayo, Cristian, Yim, Sun Young, Lee, Ju-Seog, Ivan, Cristina, Hu, Wei, Lopez-Berestein, Gabriel, Wong, Stephen T., Karlan, Beth Y., Levine, Douglas A., Liu, Jinsong, Afshar-Kharghan, Vahid, Sood, Anil K.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 21.08.2017
Nature Publishing Group
Nature Portfolio
Subjects:
631/67/1517/1709
631/80/304
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Animals
Anoikis
Blood Platelets - cytology
Blood Platelets - metabolism
Cancer
Cell Line, Tumor
Coculture Techniques
Female
Gene Expression Profiling - methods
Humanities and Social Sciences
Humans
Metastases
Metastasis
Mice, Inbred C57BL
Mice, Nude
multidisciplinary
Neoplasm Metastasis
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Phosphoproteins - genetics
Phosphoproteins - metabolism
Platelets
RhoA protein
RNA Interference
Science
Science (multidisciplinary)
Signal Transduction
Transcription Factors
Translocation
Transplantation, Heterologous
Tumors
YAP-Signaling Proteins
Yes-associated protein
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. Platelets have been associated with increased tumor growth and metastasis but the mechanistic details of this interaction are still unclear. Here the authors show that platelets improve anoikis resistance of cancer cells and increase metastasis by activating Yap through a RhoA/MYPT-PP1 pathway.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-017-00411-z