Platelets reduce anoikis and promote metastasis by activating YAP1 signaling. Nat Commun 2017 Aug 21;8(1):310
Date
08/23/2017Pubmed ID
28827520Pubmed Central ID
PMC5566477DOI
10.1038/s41467-017-00411-zScopus ID
2-s2.0-85027837141 (requires institutional sign-in at Scopus site) 165 CitationsAbstract
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.
Author List
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, Karlan BY, Levine DA, Liu J, Afshar-Kharghan V, Sood AKAuthor
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAnimals
Anoikis
Blood Platelets
Cell Line, Tumor
Coculture Techniques
Female
Gene Expression Profiling
Humans
Mice, Inbred C57BL
Mice, Nude
Neoplasm Metastasis
Ovarian Neoplasms
Phosphoproteins
RNA Interference
Signal Transduction
Transcription Factors
Transplantation, Heterologous
