Platelets reduce anoikis and promote metastasis by activating YAP1 signaling.,Nature Communications

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Platelets reduce anoikis and promote metastasis by activating YAP1 signaling.
Nature Communications ( IF 14.7 ) Pub Date : 2017-08-21 , DOI: 10.1038/s41467-017-00411-z
Monika Haemmerle _{1,

2} , Morgan L Taylor ₁ , Tony Gutschner _{3,

4} , Sunila Pradeep ₁ , Min Soon Cho ₅ , Jianting Sheng ₆ , Yasmin M Lyons ₁ , Archana S Nagaraja ₁ , Robert L Dood ₁ , Yunfei Wen ₁ , Lingegowda S Mangala _{1,

7} , Jean M Hansen ₁ , Rajesha Rupaimoole ₁ , Kshipra M Gharpure ₁ , Cristian Rodriguez-Aguayo _{7,

8} , Sun Young Yim ₉ , Ju-Seog Lee ₉ , Cristina Ivan ₈ , Wei Hu ₁ , Gabriel Lopez-Berestein _{7,

8} , Stephen T Wong ₆ , Beth Y Karlan ₁₀ , Douglas A Levine ₁₁ , Jinsong Liu ₁₂ , Vahid Afshar-Kharghan ₅ , Anil K Sood _{1,

7,

13}

Affiliation

Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Institute of Pathology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Saxony-Anhalt, 06112, Germany.
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77054, USA.
Faculty of Medicine, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Saxony-Anhalt, 06120, Germany.
Section of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, 77030, USA.
Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, 77054, USA.
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77054, USA.
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77054, USA.
Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Geffen School of Medicine at UCLA, Los Angeles, CA, 90048, USA.
Department of Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Centre, NYU Langone Medical Center, New York, NY, 10016, USA.
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77054, USA.

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.

中文翻译：

血小板可通过激活YAP1信号传导来减少失神经并促进转移。

实体恶性肿瘤患者中有30％以上存在血小板增多症，并且与患者生存期恶化相关。肿瘤细胞与肿瘤微环境的各种细胞成分（包括血小板）的相互作用对于肿瘤的生长和转移至关重要。尽管已知血小板可以渗透到肿瘤组织中，分泌促血管生成因子和促肿瘤形成因子，从而增加肿瘤的生长，但是血小板与转移性癌细胞之间的精确分子相互作用尚不清楚。在这里，我们证明了血小板在体外诱导出对神经过敏的抵抗力，并且对体内转移至关重要。我们进一步表明，血小板激活RhoA-MYPT1-PP1介导的YAP1去磷酸化并促进其核易位，从而诱导生存基因表达签名并抑制细胞凋亡。体内癌细胞中YAP1的减少可防止血小板增多症引起的转移增加。总的来说，我们的研究结果表明癌细胞依赖血小板来避免失神经并在转移过程中取得成功。血小板与肿瘤生长和转移的增加有关，但这种相互作用的机制细节尚不清楚。在这里，作者表明，血小板可以通过RhoA / MYPT-PP1途径激活Yap，从而提高癌细胞对神经缺乏的抵抗力并增加转移。血小板与肿瘤生长和转移增加有关，但这种相互作用的机制细节仍不清楚。在这里，作者表明，血小板可以通过RhoA / MYPT-PP1途径激活Yap，从而提高癌细胞对神经缺乏的抵抗力并增加转移。血小板与肿瘤生长和转移增加有关，但这种相互作用的机制细节仍不清楚。在这里，作者表明，血小板可以通过RhoA / MYPT-PP1途径激活Yap，从而提高癌细胞对神经缺乏的抵抗力并增加转移。

更新日期：2017-08-21

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