Therapeutic targeting of SPIB/SPI1‐facilitated interplay of cancer cells and neutrophils inhibits aerobic glycolysis and cancer progression

Abstract Background 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. Methods Integrative analysis of publically available expression profile datasets was used to...

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Autores principales:	Jianqun Wang, Xiaojing Wang, Yanhua Guo, Lin Ye, Dan Li, Anpei Hu, Shuang Cai, Boling Yuan, Shikai Jin, Yi Zhou, Qilan Li, Liduan Zheng, Qiangsong Tong
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	aerobic glycolysis cancer progression extracellular vesicles neutrophil Salmonella pathogenicity island 1 SPI1‐related protein Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2ce93442395040c1becf6d54d7c63e7f
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spelling	oai:doaj.org-article:2ce93442395040c1becf6d54d7c63e7f2021-11-30T07:25:38ZTherapeutic targeting of SPIB/SPI1‐facilitated interplay of cancer cells and neutrophils inhibits aerobic glycolysis and cancer progression2001-132610.1002/ctm2.588https://doaj.org/article/2ce93442395040c1becf6d54d7c63e7f2021-11-01T00:00:00Zhttps://doi.org/10.1002/ctm2.588https://doaj.org/toc/2001-1326Abstract Background 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. Methods 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. Results 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. Conclusions Therapeutic targeting of SPIB/SPI1‐facilitated interplay of cancerous cells and neutrophils suppresses aerobic glycolysis and progression of cancer.Jianqun WangXiaojing WangYanhua GuoLin YeDan LiAnpei HuShuang CaiBoling YuanShikai JinYi ZhouQilan LiLiduan ZhengQiangsong TongWileyarticleaerobic glycolysiscancer progressionextracellular vesiclesneutrophilSalmonella pathogenicity island 1SPI1‐related proteinMedicine (General)R5-920ENClinical and Translational Medicine, Vol 11, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	aerobic glycolysis cancer progression extracellular vesicles neutrophil Salmonella pathogenicity island 1 SPI1‐related protein Medicine (General) R5-920
spellingShingle	aerobic glycolysis cancer progression extracellular vesicles neutrophil Salmonella pathogenicity island 1 SPI1‐related protein Medicine (General) R5-920 Jianqun Wang Xiaojing Wang Yanhua Guo Lin Ye Dan Li Anpei Hu Shuang Cai Boling Yuan Shikai Jin Yi Zhou Qilan Li Liduan Zheng Qiangsong Tong Therapeutic targeting of SPIB/SPI1‐facilitated interplay of cancer cells and neutrophils inhibits aerobic glycolysis and cancer progression
description	Abstract Background 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. Methods 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. Results 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. Conclusions Therapeutic targeting of SPIB/SPI1‐facilitated interplay of cancerous cells and neutrophils suppresses aerobic glycolysis and progression of cancer.
format	article
author	Jianqun Wang Xiaojing Wang Yanhua Guo Lin Ye Dan Li Anpei Hu Shuang Cai Boling Yuan Shikai Jin Yi Zhou Qilan Li Liduan Zheng Qiangsong Tong
author_facet	Jianqun Wang Xiaojing Wang Yanhua Guo Lin Ye Dan Li Anpei Hu Shuang Cai Boling Yuan Shikai Jin Yi Zhou Qilan Li Liduan Zheng Qiangsong Tong
author_sort	Jianqun Wang
title	Therapeutic targeting of SPIB/SPI1‐facilitated interplay of cancer cells and neutrophils inhibits aerobic glycolysis and cancer progression
title_short	Therapeutic targeting of SPIB/SPI1‐facilitated interplay of cancer cells and neutrophils inhibits aerobic glycolysis and cancer progression
title_full	Therapeutic targeting of SPIB/SPI1‐facilitated interplay of cancer cells and neutrophils inhibits aerobic glycolysis and cancer progression
title_fullStr	Therapeutic targeting of SPIB/SPI1‐facilitated interplay of cancer cells and neutrophils inhibits aerobic glycolysis and cancer progression
title_full_unstemmed	Therapeutic targeting of SPIB/SPI1‐facilitated interplay of cancer cells and neutrophils inhibits aerobic glycolysis and cancer progression
title_sort	therapeutic targeting of spib/spi1‐facilitated interplay of cancer cells and neutrophils inhibits aerobic glycolysis and cancer progression
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/2ce93442395040c1becf6d54d7c63e7f
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Therapeutic targeting of SPIB/SPI1‐facilitated interplay of cancer cells and neutrophils inhibits aerobic glycolysis and cancer progression

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