Therapeutic targeting of SPIB/SPI1-facilitated interplay of cancer cells and neutrophils inhibits aerobic glycolysis and cancer progression.
Therapeutic targeting of SPIB/SPI1-facilitated interplay of cancer cells and neutrophils inhibits aerobic glycolysis and cancer progression.
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SPIB/SPI1 促进癌细胞和中性粒细胞相互作用的治疗靶向抑制有氧糖酵解和癌症进展
DOI：
10.1002/ctm2.588
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发表时间：
2021-11
影响因子：
10.6
通讯作者：
Tong Q
中科院分区：
文献类型：
--
作者：
Wang J;Wang X;Guo Y;Ye L;Li D;Hu A;Cai S;Yuan B;Jin S;Zhou Y;Li Q;Zheng L;Tong Q
作为一种代谢重编程特征，癌细胞从有氧糖酵解获得大部分能量，而其调节机制和治疗策略仍然是虚幻的。整合分析化学上可用的表达谱数据集，用于确定关键的转录调控因子和它们的靶糖酵解酶。通过体外和体内实验研究了转录调控因子在肿瘤细胞中的功能和作用机制。使用Kaplan-Meier曲线和对数秩分析进行生存研究。沙门氏菌致病性岛1（SPI 1/PU.1）是一种造血转录因子，被鉴定为促进结肠癌细胞的糖酵解过程、肿瘤发生、侵袭以及转移，这与肿瘤相关中性粒细胞相互作用。从机制上讲，中性粒细胞通过细胞外囊泡传递SPI 1 mRNA，导致癌细胞SPI 1表达增强。通过与SPI 1相关蛋白（SPIB）的物理相互作用，SPI 1驱动癌细胞内糖酵解基因的表达，进而通过糖酵解代谢产物乳酸诱导中性粒细胞极化。中性粒细胞的耗竭或癌细胞中SPIB-SPI 1相互作用显著抑制糖酵解过程、肿瘤发生和侵袭性。发现SPI 1或SPIB的上调与患有结肠癌的患者的不良预后相关。SPIB/SPI 1的治疗靶向促进癌细胞和中性粒细胞的相互作用，抑制有氧糖酵解和癌症的进展。转录因子SPI 1通过上调癌细胞中的HK 2和PGK 1促进有氧糖酵解。中性粒细胞通过SPI 1促进的糖酵解极化，进而通过细胞外囊泡将SPI 1 mRNA递送到癌细胞中。SPIB通过在癌细胞中的物理相互作用促进SPI 1反式激活。SPIB-SPI 1相互作用或中性粒细胞的治疗靶向抑制有氧糖酵解和癌症进展。
As a metabolic reprogramming feature, cancer cells derive most of their energy from aerobic glycolysis, while its regulatory mechanisms and therapeutic strategies continue to be illusive. Integrative analysis of publically available expression profile datasets was used to identify critical transcriptional regulators and their target glycolytic enzymes. The functions and acting mechanisms of transcriptional regulators in cancer cells were investigated by using in vitro and in vivo assays. The Kaplan–Meier curve and log‐rank assay were used to conduct the survival study. Salmonella pathogenicity island 1 (SPI1/PU.1), a haematopoietic transcription factor, was identified to facilitate glycolytic process, tumourigenesis, invasiveness, as well as metastasis of colon cancer cells, which was interplayed by tumour‐associated neutrophils. Mechanistically, neutrophils delivered SPI1 mRNA via extracellular vesicles, resulting in enhanced SPI1 expression of cancer cells. Through physical interaction with SPI1‐related protein (SPIB), SPI1 drove expression of glycolytic genes within cancer cells, which in turn induced polarization of neutrophils via glycolytic metabolite lactate. Depletion of neutrophils or SPIB–SPI1 interaction in cancer cells significantly inhibited glycolytic process, tumourigenesis and aggressiveness. Upregulation of SPI1 or SPIB was found to be associated with poor prognosis in patients suffering from colon cancer. Therapeutic targeting of SPIB/SPI1‐facilitated interplay of cancerous cells and neutrophils suppresses aerobic glycolysis and progression of cancer. Transcription factor SPI1 promotes aerobic glycolysis via upregulating HK2 and PGK1 in cancer cells. Neutrophils are polarized by SPI1‐facilitated glycolysis, which in turn deliver SPI1 mRNA into cancer cells via extracellular vesicles. SPIB facilitates SPI1 transactivation via physical interaction in cancer cells. Therapeutic targeting of SPIB–SPI1 interaction or neutrophils inhibits aerobic glycolysis and cancer progression.
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影响因子：
50.3
作者：
Granot Z;Henke E;Comen EA;King TA;Norton L;Benezra R
通讯作者：
Benezra R
影响因子：
20.3
作者：
Federzoni, Elena A.;Valk, Peter J. M.;Tschan, Mario P.
通讯作者：
Tschan, Mario P.
影响因子：
5.8
作者：
Lachmann, Alexander;Xu, Huilei;Ma'ayan, Avi
通讯作者：
Ma'ayan, Avi
MZF1-AS1/PARP1/E2F1 轴的治疗靶向抑制脯氨酸合成和神经母细胞瘤进展
影响因子：
15.1
作者：
Fang, Erhu;Wang, Xiaojing;Tong, Qiangsong
通讯作者：
Tong, Qiangsong
DOI：
10.1111/j.1365-2613.2007.00539.x
发表时间：
2007-10-01
影响因子：
3
作者：
DuPre, Sally A.;Redelman, Doug;Hunter, Kenneth W., Jr.
通讯作者：
Hunter, Kenneth W., Jr.