Fyn knockdown inhibits migration and invasion in cholangiocarcinoma through the activated AMPK/mTOR signaling pathway.
Fyn knockdown inhibits migration and invasion in cholangiocarcinoma through the activated AMPK/mTOR signaling pathway.
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Fyn敲低抑制了通过激活的AMPK/MTOR信号通路的胆管癌中的迁移和侵袭。
DOI：
10.3892/ol.2017.7542
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发表时间：
2018-03
期刊：
影响因子：
2.9
通讯作者：
He Q
中科院分区：
文献类型：
--
作者：
Lyu SC;Han DD;Li XL;Ma J;Wu Q;Dong HM;Bai C;He Q
胆管癌是一种罕见而致命的肿瘤。在过去的几十年里，这种肿瘤的发病率和死亡率在全球范围内稳步上升。转移被认为是导致CCA患者预后不良的主要因素。因此，研究旨在开发新的治疗靶点来控制CCA转移。已知Fyn在各种癌症中增强表达并促进转移，包括胰腺癌、前列腺癌和结肠直肠癌。然而，Fyn在CCA转移中的确切功能和机制尚不清楚。本研究采用逆转录-定量聚合酶链反应（RT-PCR）和蛋白质印迹法（Western blot）检测了CCA组织和细胞系中Fyn、AMP活化蛋白激酶（AMPK）、磷酸化（p-）AMPK、哺乳动物雷帕霉素靶蛋白（mTOR）和p-mTOR的mRNA和蛋白表达水平。此外，使用Transwell测定来确定转染后人CCA QBC 939的迁移和侵袭能力。在本研究中，发现Fyn在CCA细胞系中过表达。Fyn敲低抑制CCA细胞迁移和侵袭。此外，已经证明Fyn敲低诱导AMPK的磷酸化，抑制mTOR的下游磷酸化，并激活AMPK/mTOR信号通路。AMPK抑制剂化合物C抑制AMPK/mTOR信号通路，并逆转Fyn敲低对CCA细胞迁移和侵袭的影响。总之，本研究表明，Fyn敲低通过调节CCA细胞系中AMPK/mTOR信号通路来抑制细胞迁移和侵袭，并且Fyn敲低是抗CCA治疗的潜在靶点。
Cholangiocarcinoma (CCA) is a rare and fatal tumor. In previous decades, there has been a steady increase in the incidence and mortality rates of this tumor worldwide. Metastasis is regarded as the major factor that contributes to poor prognosis in CCA patients. Studies therefore aim to develop novel therapeutic targets to control CCA metastasis. Fyn is known to enhance expression and promote metastasis in various cancers, including pancreatic cancer, prostate cancer and colorectal cancer. However, the exact function and mechanism of Fyn in CCA metastasis remains unclear. In the present study, mRNA and protein expression levels of Fyn, AMP-activated protein kinase (AMPK), phosphorylated (p-)AMPK, mammalian target of rapamycin (mTOR) and p-mTOR were measured, using the reverse transcription-quantitative polymerase chain reaction and western blot analysis, in CCA tissues and cell lines. In addition, Transwell assays were used to determine the migratory and invasive abilities of human CCA QBC939, following transfection. In the present study, it was found that Fyn was overexpressed in CCA cell lines. Fyn knockdown inhibited CCA cell migration and invasion. Furthermore, it was demonstrated that Fyn knockdown induces phosphorylation of AMPK, inhibits downstream phosphorylation of mTOR, and activate the AMPK/mTOR signaling pathway. Compound C, an AMPK inhibitor, inhibited the AMPK/mTOR signaling pathway, and reversed the effect of Fyn knockdown on migration and invasion of CCA cells. In conclusion, the present study suggests that Fyn knockdown inhibits cell migration and invasion by regulating the AMPK/mTOR signaling pathway in CCA cell lines and that Fyn knockdown is a potential target for anti-CCA therapy.
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影响因子：
12.8
作者：
Song JL;Zheng W;Chen W;Qian Y;Ouyang YM;Fan CY
通讯作者：
Fan CY
影响因子：
3.1
作者：
Tyson GL;Ilyas JA;Duan Z;Green LK;Younes M;El-Serag HB;Davila JA
通讯作者：
Davila JA
影响因子：
254.7
作者：
Torre, Lindsey A.;Bray, Freddie;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
DOI：
10.1111/1440-1681.12409
发表时间：
2015-06-01
影响因子：
2.9
作者：
Li, Hong-Xia;Gao, Jing-Miao;Wu, Yong-Jie
通讯作者：
Wu, Yong-Jie
Fyn 需要 HnRNPA2B1 和 Sam68 协同调节胰腺癌细胞凋亡
影响因子：
4.7
作者：
Chen, Zhi-Yu;Cai, Lei;Li, Xiao-Wu
通讯作者：
Li, Xiao-Wu