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-BeresteinStephen T. Wong, Beth Y. Karlan, Douglas A. Levine, Jinsong Liu, Vahid Afshar-Kharghan, Anil K. Sood

Research output: Contribution to journalArticle

73 Scopus citations

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.

Original languageEnglish (US)
Article number310
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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