TY - JOUR
T1 - Effects and related mechanisms of serotonin on malignant biological behavior of hepatocellular carcinoma via regulation of Yap
AU - Liu, Sushun
AU - Miao, Runchen
AU - Zhai, Mimi
AU - Pang, Qing
AU - Deng, Yan
AU - Liu, Sinan
AU - Qu, Kai
AU - Liu, Chang
AU - Zhang, Jingyao
N1 - Publisher Copyright:
© Liu et al.
PY - 2017
Y1 - 2017
N2 - 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 5-5-HT2BR to promote Yap expression via upregulating the pERK level. Inhibitors of 5-5-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.
AB - 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 5-5-HT2BR to promote Yap expression via upregulating the pERK level. Inhibitors of 5-5-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.
KW - 5-5-HTR
KW - 5-HT
KW - ERK
KW - Hepatocellular carcinoma
KW - Yap
UR - https://www.scopus.com/pages/publications/85024408440
U2 - 10.18632/oncotarget.17658
DO - 10.18632/oncotarget.17658
M3 - 文章
C2 - 28537892
AN - SCOPUS:85024408440
SN - 1949-2553
VL - 8
SP - 47412
EP - 47424
JO - Oncotarget
JF - Oncotarget
IS - 29
ER -