Reprogramming of Energy Metabolism: Increased Expression and Roles of Pyruvate Carboxylase in Papillary Thyroid Cancer

柠檬酸循环 瓦博格效应 下调和上调 丙酮酸羧化酶 甲状腺癌 甲状腺乳突癌 癌细胞 间质细胞 糖酵解 生物 细胞周期 癌症研究 化学 新陈代谢 癌症 生物化学 甲状腺 细胞 内分泌学 基因 遗传学
作者
Aurélie Strickaert,Cyril Corbet,Selim-Alex Spinette,Ligia Craciun,Geert Dom,Guy Andry,Denis Larsimont,Ruddy Wattiez,Jacques Emile Dumont,Olivier Féron,Carine Maenhaut
出处
期刊:Thyroid [Mary Ann Liebert]
卷期号:29 (6): 845-857 被引量:34
标识
DOI:10.1089/thy.2018.0435
摘要

Background: Energy metabolism is described to be deregulated in cancer, and the Warburg effect is considered to be a major hallmark. Recently, cellular heterogeneity in tumors and the tumor microenvironment has been recognized to play an important role in several metabolic pathways in cancer. However, its contribution to papillary thyroid cancer (PTC) development and metabolism is still poorly understood. Methods: A proteomic analysis of five PTC was performed, and the cellular distribution of several upregulated metabolic proteins was investigated in the cancerous and stromal cells of these tumors. Results: Tandem mass spectrometry analysis revealed the upregulation of many metabolism-related proteins, among them pyruvate carboxylase (PC). PC knockdown in thyroid cell lines alters their proliferative and motility capacities, and measurements of oxygen consumption rates show that this enzyme is involved in the replenishment of the tricarboxylic acid cycle. Immunostainings of several upregulated metabolic proteins show that thyroid cancer cells have an increased mitochondrial oxidative metabolism compared to stromal cells. Conclusions: PTC has a very active tricarboxylic acid cycle, continuously replenished by a PC-mediated anaplerosis. This is specifically observed in the tumor cells.
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