Platelets reduce anoikis and promote metastasis by activating YAP1 signaling

被引:201
作者
Haemmerle, Monika [1 ,2 ]
Taylor, Morgan L. [1 ]
Gutschner, Tony [3 ,4 ]
Pradeep, Sunila [1 ]
Cho, Min Soon [5 ]
Sheng, Jianting [6 ]
Lyons, Yasmin M. [1 ]
Nagaraja, Archana S. [1 ]
Dood, Robert L. [1 ]
Wen, Yunfei [1 ]
Mangala, Lingegowda S. [1 ,7 ]
Hansen, Jean M. [1 ]
Rupaimoole, Rajesha
Gharpure, Kshipra M. [1 ]
Rodriguez-Aguayo, Cristian [7 ,8 ]
Yim, Sun Young [9 ]
Lee, Ju-Seog [9 ]
Ivan, Cristina [8 ]
Hu, Wei [1 ]
Lopez-Berestein, Gabriel [7 ,8 ]
Wong, Stephen T. [6 ]
Karlan, Beth Y. [10 ]
Levine, Douglas A. [11 ]
Liu, Jinsong [12 ]
Afshar-Kharghan, Vahid [5 ]
Sood, Anil K. [1 ,7 ,13 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA
[2] Martin Luther Univ Halle Wittenberg, Inst Pathol, D-06112 Halle An Der Saale, Saxony Anhalt, Germany
[3] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77054 USA
[4] Martin Luther Univ Halle Wittenberg, Fac Med, D-06120 Halle An Der Saale, Saxony Anhalt, Germany
[5] Univ Texas MD Anderson Canc Ctr, Sect Benign Hematol, Houston, TX 77030 USA
[6] Houston Methodist Hosp, Houston Methodist Res Inst, Dept Syst Med & Bioengn, Houston, TX 77030 USA
[7] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNA, Houston, TX 77054 USA
[8] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77054 USA
[9] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77054 USA
[10] UCLA, Geffen Sch Med, Cedars Sinai Med Ctr, Dept Obstet & Gynecol, Los Angeles, CA 90048 USA
[11] NYU, Langone Med Ctr, Dept Gynecol Oncol, Laura & Isaac Perlmutter Canc Ctr, New York, NY 10016 USA
[12] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
[13] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77054 USA
基金
美国国家卫生研究院;
关键词
HIPPO PATHWAY; POOR-PROGNOSIS; PARANEOPLASTIC THROMBOCYTOSIS; PROTEIN PHOSPHATASE; MYOSIN PHOSPHATASE; CANCER METASTASIS; INHIBITION; GROWTH; PROLIFERATION; INVOLVEMENT;
D O I
10.1038/s41467-017-00411-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:15
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