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illusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2013Meier curve and log\u2010rank assay were used to conduct the survival study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2010associated neutrophils. Mechanistically, neutrophils delivered <jats:italic>SPI1<\/jats:italic> mRNA via extracellular vesicles, resulting in enhanced <jats:italic>SPI1<\/jats:italic> expression of cancer cells. Through physical interaction with SPI1\u2010related 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\u2013SPI1 interaction in cancer cells significantly inhibited glycolytic process, tumourigenesis and aggressiveness. Upregulation of <jats:italic>SPI1<\/jats:italic> or <jats:italic>SPIB<\/jats:italic> was found to be associated with poor prognosis in patients suffering from colon cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Therapeutic targeting of <jats:italic>SPIB<\/jats:italic>\/<jats:italic>SPI1<\/jats:italic>\u2010facilitated interplay of cancerous cells and neutrophils suppresses aerobic glycolysis and progression of cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.588","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T08:16:50Z","timestamp":1636013810000},"source":"Crossref","is-referenced-by-count":54,"title":["Therapeutic targeting of <i>SPIB<\/i>\/<i>SPI1<\/i>\u2010facilitated interplay of cancer cells and neutrophils inhibits aerobic glycolysis and cancer progression"],"prefix":"10.1002","volume":"11","author":[{"given":"Jianqun","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  1277 Jiefang Avenue Wuhan Hubei Province 430022 P. 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