The TRPM7 channel reprograms cellular glycolysis to drive tumorigenesis and angiogenesis.
The TRPM7 channel reprograms cellular glycolysis to drive tumorigenesis and angiogenesis.
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TRPM7通道对细胞糖酵解进行重新编程，以驱动肿瘤发生和血管生成。
DOI：
10.1038/s41419-023-05701-7
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发表时间：
2023-03-06
影响因子：
9
通讯作者：
Bai, Yongping
中科院分区：
文献类型：
--
作者：
Wu, Wanzhou;Wang, Xuan;Liao, Longsheng;Chen, Jing;Wang, Yue;Yao, Meilian;Zhu, Lingping;Li, Jiayu;Chen, Alex F.;Zhang, Guogang;Zhang, Zheng;Bai, Yongping
癌症或内皮细胞优选通过有氧糖酵解而不是氧化磷酸化来分解代谢葡萄糖。细胞内离子信号已被证明可以调节葡萄糖代谢，但潜在的离子通道尚未确定。RNA-seq、代谢组学和遗传分析表明TRPM 7通道调节细胞糖酵解。TRPM 7的缺失抑制癌细胞糖酵解并降低异种移植肿瘤负荷。内皮TRPM 7缺陷抑制小鼠出生后视网膜血管生成。TRPM 7通过Ca 2+内流诱导的钙调磷酸酶激活转录调节溶质载体家族2成员3（SLC 2A 3，也称为GLUT 3）。此外，CREB调节的转录辅激活因子2（CRTC 2）和CREB在钙调磷酸酶下游起作用，将Ca 2+信号传递到SLC 2A 3转录。TRPM 7敲除细胞中组成型活性CRTC 2或CREB的表达使糖酵解代谢和细胞生长正常化。TRPM 7通道代表糖酵解重编程的新调节剂。TRPM 7依赖性糖酵解的抑制可以用于癌症治疗。
Cancer or endothelial cells preferably catabolize glucose through aerobic glycolysis rather than oxidative phosphorylation. Intracellular ionic signaling has been shown to regulate glucose metabolism, but the underlying ion channel has yet to be identified. RNA-seq, metabolomics and genetic assay revealed that the TRPM7 channel regulated cellular glycolysis. Deletion of TRPM7 suppressed cancer cell glycolysis and reduced the xenograft tumor burden. Deficiency of endothelial TRPM7 inhibited postnatal retinal angiogenesis in mice. Mechanistically, TRPM7 transcriptionally regulated the solute carrier family 2 member 3 (SLC2A3, also known as GLUT3) via Ca2+ influx-induced calcineurin activation. Furthermore, CREB-regulated transcription coactivator 2 (CRTC2) and CREB act downstream of calcineurin to relay Ca2+ signal to SLC2A3 transcription. Expression of the constitutively active CRTC2 or CREB in TRPM7 knockout cell normalized glycolytic metabolism and cell growth. The TRPM7 channel represents a novel regulator of glycolytic reprogramming. Inhibition of the TRPM7-dependent glycolysis could be harnessed for cancer therapy.
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影响因子：
64.5
作者：
De Bock, Katrien;Georgiadou, Maria;Carmeliet, Peter
通讯作者：
Carmeliet, Peter
影响因子：
37.8
作者：
Sah R;Mesirca P;Mason X;Gibson W;Bates-Withers C;Van den Boogert M;Chaudhuri D;Pu WT;Mangoni ME;Clapham DE
通讯作者：
Clapham DE
影响因子：
50.3
作者：
Cantelmo AR;Conradi LC;Brajic A;Goveia J;Kalucka J;Pircher A;Chaturvedi P;Hol J;Thienpont B;Teuwen LA;Schoors S;Boeckx B;Vriens J;Kuchnio A;Veys K;Cruys B;Finotto L;Treps L;Stav-Noraas TE;Bifari F;Stapor P;Decimo I;Kampen K;De Bock K;Haraldsen G;Schoonjans L;Rabelink T;Eelen G;Ghesquière B;Rehman J;Lambrechts D;Malik AB;Dewerchin M;Carmeliet P
通讯作者：
Carmeliet P
影响因子：
20.1
作者：
Du J;Xie J;Zhang Z;Tsujikawa H;Fusco D;Silverman D;Liang B;Yue L
通讯作者：
Yue L
影响因子：
82.9
作者：
Ikeda K;Kang Q;Yoneshiro T;Camporez JP;Maki H;Homma M;Shinoda K;Chen Y;Lu X;Maretich P;Tajima K;Ajuwon KM;Soga T;Kajimura S
通讯作者：
Kajimura S