TAp73-induced phosphofructokinase-1 transcription promotes the Warburg effect and enhances cell proliferation.
TAp73-induced phosphofructokinase-1 transcription promotes the Warburg effect and enhances cell proliferation.
复制标题
TAp73 诱导的磷酸果糖激酶-1 转录可促进 Warburg 效应并增强细胞增殖。
DOI：
10.1038/s41467-018-07127-8
复制
发表时间：
2018-11-08
影响因子：
16.6
通讯作者：
Jiang P
中科院分区：
文献类型：
--
作者：
Li L;Li L;Li W;Chen T;Bin Zou;Zhao L;Wang H;Wang X;Xu L;Liu X;Wang D;Li B;Mak TW;Du W;Yang X;Jiang P
Warburg效应是与肿瘤疾病相关的一个显著代谢特征；然而，潜在的机制仍然不完全清楚。TAp73是肿瘤抑制因子p53的结构同源物，在人类肿瘤中经常过表达，这表明它可以赋予肿瘤细胞增殖优势。本研究表明，TAp73可以刺激肝型磷酸果糖激酶-1 （PFKL）的表达，从而催化糖酵解的特定步骤。通过这种调节，TAp73增加葡萄糖消耗和乳酸排泄，促进Warburg效应。通过激活PFKL， TAp73也增加ATP的产生和增强抗氧化防御。TAp73缺乏导致致瘤潜能显著降低，这可以通过强迫PFKL表达来挽救。这些发现证实了TAp73是糖酵解的关键调节因子，并揭示了肿瘤细胞实现Warburg效应以促进致癌生长的机制。TAp73是肿瘤抑制因子p53的结构同源物。在这里，他们表明TAp73对促进糖酵解至关重要，因为它刺激肝脏型磷酸果糖激酶-1 （PFKL）的转录表达，而PFKL催化糖酵解的承诺步骤。
The Warburg effect is a prominent metabolic feature associated with neoplastic diseases; however, the underlying mechanism remains incompletely understood. TAp73, a structural homolog of the tumor suppressor p53, is frequently overexpressed in human tumors, indicating a proliferative advantage that it can confer to tumor cells. Here we show that TAp73 stimulates the expression of phosphofructokinase-1, liver type (PFKL), which catalyzes the committed step in glycolysis. Through this regulation, TAp73 enhances glucose consumption and lactate excretion, promoting the Warburg effect. By activating PFKL, TAp73 also increases ATP production and bolsters anti-oxidant defense. TAp73 deficiency results in a pronounced reduction in tumorigenic potential, which can be rescued by forced PFKL expression. These findings establish TAp73 as a critical regulator of glycolysis and reveal a mechanism by which tumor cells achieve the Warburg effect to enable oncogenic growth. TAp73 is a structural homolog of the tumor suppressor p53. Here they show that TAp73 is critical for promoting glycolysis as it stimulates the transcriptional expression of liver type of phosphofructokinase-1 (PFKL), which catalyzes the committed step in glycolysis.
登录
查看更多内容
影响因子：
13.8
作者：
Liberti MV;Locasale JW
通讯作者：
Locasale JW
影响因子：
13.8
作者：
Patra, Krushna C.;Hay, Nissim
通讯作者：
Hay, Nissim
影响因子：
--
作者：
Ayyoob, Khosravi;Masoud, Khoshnia;Jahanbakhsh, Asadi
通讯作者：
Jahanbakhsh, Asadi
影响因子：
9.3
作者：
Ben-Haim, Simona;Ell, Peter
通讯作者：
Ell, Peter
p53和苹果酶的相互调节调节新陈代谢和衰老。
影响因子：
64.8
作者：
通讯作者：
--