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血清素通过调控Yap对肝细胞癌恶性生物学行为的影响及相关机制

Effects and related mechanisms of serotonin on malignant biological behavior of hepatocellular carcinoma via regulation of Yap.

作者信息

Liu Sushun, Miao Runchen, Zhai Mimi, Pang Qing, Deng Yan, Liu Sinan, Qu Kai, Liu Chang, Zhang Jingyao

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

出版信息

Oncotarget. 2017 Jul 18;8(29):47412-47424. doi: 10.18632/oncotarget.17658.

DOI:10.18632/oncotarget.17658
PMID:28537892
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5564575/
Abstract

5-hydroxytryptamine (5-HT, serotonin) and Yes-associated protein (Yap), which act as a mitogen and an oncogene, respectively, play an important role in tumors. Here, we investigated whether 5-HT could affect the hepatocarcinogenic process via promoting the activation and expression of Yap, as well as the possible underlying molecular mechanisms. We found that 5-HT promoted hepatoma cell proliferation, invasion and metastasis via regulating Yap expression in vitro and in vivo, and Yap knockdown had opposite effects. Furthermore, 5-HT activated 5-HT2BR to promote Yap expression via upregulating the pERK level. Inhibitors of 5-HT2BR and ERK attenuated the overexpression of Yap and promotional effects of 5-HT in vitro and in vivo. As a result, 5-HT affected the malignant biological behavior of hepatoma cells via the 5-HT-5-HT2BR-pERK-Yap axis. Therefore, 5-HT and Yap may be prognostic predictors and potential therapeutic targets for HCC patients in the future.

摘要

5-羟色胺（5-HT，血清素）和Yes相关蛋白（Yap）分别作为一种促有丝分裂原和一种癌基因，在肿瘤中发挥重要作用。在此，我们研究了5-HT是否可通过促进Yap的激活和表达来影响肝癌致癌过程，以及可能的潜在分子机制。我们发现，5-HT在体外和体内通过调节Yap表达促进肝癌细胞增殖、侵袭和转移，而敲低Yap则产生相反的效果。此外，5-HT激活5-HT2BR以通过上调pERK水平促进Yap表达。5-HT2BR和ERK的抑制剂在体外和体内减弱了Yap的过表达以及5-HT的促进作用。结果，5-HT通过5-HT-5-HT2BR-pERK-Yap轴影响肝癌细胞的恶性生物学行为。因此，5-HT和Yap未来可能是肝癌患者的预后预测指标和潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c9/5564575/f8686ed82074/oncotarget-08-47412-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c9/5564575/970d790c8cfa/oncotarget-08-47412-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c9/5564575/ca7904e813a9/oncotarget-08-47412-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c9/5564575/f8686ed82074/oncotarget-08-47412-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c9/5564575/f2aa4d91dc05/oncotarget-08-47412-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c9/5564575/a952ef12ec2b/oncotarget-08-47412-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c9/5564575/adb96371ca82/oncotarget-08-47412-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c9/5564575/af11529e571e/oncotarget-08-47412-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c9/5564575/a7bd963c9064/oncotarget-08-47412-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c9/5564575/970d790c8cfa/oncotarget-08-47412-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c9/5564575/ca7904e813a9/oncotarget-08-47412-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c9/5564575/f8686ed82074/oncotarget-08-47412-g008.jpg

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