Cpt1c regulated by AMPK promotes papillary thyroid carcinomas cells survival under metabolic stress conditions.
Cpt1c regulated by AMPK promotes papillary thyroid carcinomas cells survival under metabolic stress conditions.
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AMPK调节的Cpt1c促进代谢应激条件下甲状腺乳头状癌细胞的存活
DOI：
10.7150/jca.21148
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发表时间：
2017
影响因子：
3.9
通讯作者：
Yao Z
中科院分区：
文献类型：
--
作者：
Wang R;Cheng Y;Su D;Gong B;He X;Zhou X;Pang Z;Cheng L;Chen Y;Yao Z
背景：癌细胞在肿瘤发展过程中需要增加能量和充足的血管形成，因此需要进行代谢转化。然而，分子机制尚不完全清楚。在本研究中，我们发现肉碱棕榈酰基转移酶1C （Cpt1c）作为gate-keeper酶的一员，在AMPK的调控下将长链脂肪酸转移到线粒体进一步氧化，从而促进代谢应激条件下甲状腺乳头状癌细胞的存活。方法：首先采用qRT-PCR检测甲状腺乳头状癌组织与配对正常组织中Cpt1c的表达。其次，建立缺氧（0.2%氧）和葡萄糖剥夺培养的甲状腺乳头状癌细胞模型，以评估代谢应激是否会诱导Cpt1c。最后，用AICAR （AMPK的激动剂）和Compound C （AMPK的抑制剂）处理KTC-1细胞，研究代谢应激下AMPK活性与Cpt1c表达的相关性。结果：甲状腺乳头状癌组织中Cpt1c高于配对正常组织。此外，Cpt1c的上调促进了癌细胞的生长和转移。此外，结果表明Cpt1c表达受代谢应激诱导，包括缺氧和低糖处理。Cpt1c可以保护细胞免受缺氧和低糖引起的癌细胞死亡。最后，Cpt1c的表达受AMPK活性的调控。结论：在甲状腺乳头状癌中，面对代谢应激的Cpt1c表达的诱导至少部分受到AMPK活性的调节，并最终促进了甲状腺乳头状癌的发生和进展。
Background: Cancer cells have to take metabolic transformation in tumor progression when facing need of increased energy and adequate vascularization. However, molecular mechanism is not fully known. In this study, we showed that expression of carnitine palmitoyltransferase 1C (Cpt1c), as a member of the gate-keeper enzymes , which transferring long-chain fatty acids into mitochondria to further oxidation, which is regulated by AMPK promotes papillary thyroid carcinomas cells survival under metabolic stress conditions. Methods: Firstly, we used qRT-PCR to detect expression of Cpt1c in papillary thyroid carcinomas tissues compared with paired normal tissues. Secondly, to evaluate whether Cpt1c is induced under metabolic stress, models of hypoxia (0.2% oxygen) and glucose deprivation for cultured papillary thyroid carcinomas cells were established. Lastly, KTC-1 cells were treated with AICAR (as an agonist of AMPK) and Compound C (as an inhibitor of AMPK) to investigate the correlation of AMPK activity with Cpt1c expression under metabolic stress. Results: Cpt1c is higher in papillary thyroid carcinomas tissues compared with paired normal tissues. Furthermore, Cpt1c up-regulation promotes cancer cell growth and metastasis. In addition, the results showed that Cpt1c expression is induced by metabolic stress, including hypoxia and low glucose treatment. Consistently, Cpt1c can protect cells from cancer cells death caused by hypoxia and low glucose. Lastly, Cpt1c expression is regulated by AMPK activity. Conclusion: Here we describe that induction of Cpt1c expression facing metabolic stress in papillary thyroid carcinomas is at least partly regulated by AMPK activity and ultimately contribute to development and progression of papillary thyroid carcinomas.
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影响因子：
10.1
作者：
Hossain, Fokhrul;Al-Khami, Amir A.;Ochoa, Augusto C.
通讯作者：
Ochoa, Augusto C.
影响因子：
15.9
作者：
Samudio, Ismael;Harmancey, Romain;Andreeff, Michael
通讯作者：
Andreeff, Michael
影响因子：
4.6
作者：
Lee H;Oh ET;Choi BH;Park MT;Lee JK;Lee JS;Park HJ
通讯作者：
Park HJ
影响因子：
10.5
作者：
Zaugg, Kathrin;Yao, Yi;Mak, Tak W.
通讯作者：
Mak, Tak W.
影响因子：
29
作者：
Kim, JW;Tchernyshyov, I;Dang, CV
通讯作者：
Dang, CV