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Platelets reduce anoikis and promote metastasis by activating YAP1 signaling.

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.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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Haemmerle M,Taylor ML,Gutschner T,Pradeep S,Cho MS,Sheng J,Lyons YM,Nagaraja AS,Dood RL,Wen Y,Mangala LS,Hansen JM,Rupaimoole R,Gharpure KM,Rodriguez-Aguayo C,Yim SY,Lee JS,Ivan C,Hu W,Lopez-Berestein G,Wong ST,

doi

10.1038/s41467-017-00411-z

subject

Has Abstract

pub_date

2017-08-21 00:00:00

pages

310

issue

1

issn

2041-1723

pii

10.1038/s41467-017-00411-z

journal_volume

8

pub_type

杂志文章

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