Pyruvate carboxylase promotes malignant transformation of papillary thyroid carcinoma and reduces iodine uptake.
Pyruvate carboxylase promotes malignant transformation of papillary thyroid carcinoma and reduces iodine uptake.
复制标题
DOI：
10.1038/s41420-022-01214-y
复制
发表时间：
2022-10-20
影响因子：
7
通讯作者：
Zhang, Yifan
中科院分区：
文献类型：
--
作者：
Liu, Yang;Liu, Chang;Pan, Yu;Zhou, Jinxin;Ju, Huijun;Zhang, Yifan
前期研究表明丙酮酸羧化酶（PC）在甲状腺癌（TC）的发生、进展中发挥关键作用；然而，PC 与碘难治性 TC 之间的关系尚不清楚。因此，本研究旨在探讨PC在乳头状TC（PTC）恶性进展和碘摄取丧失中的分子机制，并探讨PC抑制剂对碘难治性PTC的潜在治疗作用。 PC 增加细胞增殖、侵袭和转移，抑制碘代谢相关基因 TSHR、NIS、TPO 和 TG 的表达，并通过激活 PTC 细胞系中丝裂原激活蛋白激酶/细胞外信号调节激酶途径降低碘摄取能力。此外，PC抑制剂ZY-444有效抑制PC的活化，降低恶性侵袭能力，恢复PTC细胞碘代谢相关基因的表达和摄碘能力。这些发现表明，PC 激活参与了碘难治性 TC 的进展，PC 抑制剂可能代表了一种潜在的新型碘难治性 TC 靶向治疗方法。
Previous studies have shown that pyruvate carboxylase (PC) plays a key role in the occurrence and progression of thyroid cancer (TC); however, the relationship between PC and iodine-refractory TC is unclear. Therefore, the present study aimed to investigate the molecular mechanism of PC in the malignant progression and loss of iodine uptake in papillary TC (PTC) and to explore the potential therapeutic effect of PC inhibitors in iodine-refractory PTC. PC increased cell proliferation, invasion, and metastasis, inhibited expression of the iodine metabolism-related genes TSHR, NIS, TPO, and TG, and decreased the iodine-uptake capacity by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway in PTC cell lines. Furthermore, the PC inhibitor ZY-444 effectively inhibited the activation of PC, reduced the malignant invasiveness, and restored the expression of iodine metabolism-related genes and the iodine-uptake capacity in PTC cells. These findings suggest that PC activation is involved in the progression of iodine-refractory TC and that PC inhibitors may represent a potentially novel targeted therapy for iodine-refractory TC.
登录
查看更多内容
影响因子：
5.8
作者：
Durante, C.;Haddy, N.;Schlumberger, M.
通讯作者：
Schlumberger, M.
丙酮酸羧化酶通过脂肪酸合成促进甲状腺癌的侵袭性
影响因子：
3.8
作者：
Liu C;Zhou X;Pan Y;Liu Y;Zhang Y
通讯作者：
Zhang Y
甲状腺细针穿刺冲洗液中丙酮酸羧化酶对甲状腺乳头状癌淋巴结转移的预测价值
影响因子：
4.7
作者：
Liu C;Zhang L;Liu Y;Zhao Q;Pan Y;Zhang Y
通讯作者：
Zhang Y
影响因子：
37.3
作者：
Fan TW;Lane AN;Higashi RM;Farag MA;Gao H;Bousamra M;Miller DM
通讯作者：
Miller DM
影响因子：
64.5
作者：
Chio IIC;Jafarnejad SM;Ponz-Sarvise M;Park Y;Rivera K;Palm W;Wilson J;Sangar V;Hao Y;Öhlund D;Wright K;Filippini D;Lee EJ;Da Silva B;Schoepfer C;Wilkinson JE;Buscaglia JM;DeNicola GM;Tiriac H;Hammell M;Crawford HC;Schmidt EE;Thompson CB;Pappin DJ;Sonenberg N;Tuveson DA
通讯作者：
Tuveson DA