Intestinal epithelial C/EBPβ deficiency impairs colitis-associated tumorigenesis by disrupting CXCL1/CXCL2/CXCL5-CXCR2-mediated neutrophil infiltrationOA
Dysregulated transcription factors critically link chronic inflammation to oncogenesis in colitis-associated colorectal cancer(CAC),but their mechanistic roles remain incompletely understood.By integrating microarray and transcriptome sequencing data from ulcerative colitis(UC),colitis-associated cancer(CAC),and colorectal cancer(CRC)patients,we identify C/EBPβas a key transcriptional regulator whose elevated expression inversely correlates with survival.In azoxymethane(AOM)/dextran sulfate sodium(DSS)-induced CAC models,intestinal epithelial C/EBPβis upregulated during tumor progression,which is correlated with exacerbated tumor burden and neutrophil infiltration.Mice with intestinal epithelial-specific Cebpb deletion(CebpbΔIEC)are resistant to carcinogenesis,accompanied by reduced neutrophil infiltration and tumor growth.Mechanistically,C/EBPβtranscriptionally activates CXCR2 ligands(CXCL1,CXCL2,and CXCL5)to drive neutrophil recruitment.Pharmacological inhibition of CXCR2 phenocopies the anti-tumor effects of CebpbΔIEC deletion,further validating this axis as a therapeutic target.Correlation analysis of patient tissues confirms positive relationships between C/EBPβ,CXCR2 ligands,and neutrophil infiltration,suggesting that targeting the C/EBPβ-CXCL1/2/5-CXCR2 axis may constitute a novel strategy for treating CAC.
Mingyue Li;Xintong Wang;Wenjie Hu;Xiaohui Cheng;Qi Sun;Yongjie Wu;Zhen Huang;Jiangning Chen
State Key Laboratory of Analytical Chemistry for Life Sciences,School of Life Sciences,Nanjing University,Nanjing 210023,ChinaState Key Laboratory of Analytical Chemistry for Life Sciences,School of Life Sciences,Nanjing University,Nanjing 210023,ChinaState Key Laboratory of Analytical Chemistry for Life Sciences,School of Life Sciences,Nanjing University,Nanjing 210023,ChinaState Key Laboratory of Analytical Chemistry for Life Sciences,School of Life Sciences,Nanjing University,Nanjing 210023,ChinaState Key Laboratory of Analytical Chemistry for Life Sciences,School of Life Sciences,Nanjing University,Nanjing 210023,ChinaState Key Laboratory of Analytical Chemistry for Life Sciences,School of Life Sciences,Nanjing University,Nanjing 210023,ChinaState Key Laboratory of Analytical Chemistry for Life Sciences,School of Life Sciences,Nanjing University,Nanjing 210023,China State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences,Nanjing University,Nanjing 210023,China NJU Xishan Institute of Applied Biotechnology,Wuxi 214101,ChinaState Key Laboratory of Analytical Chemistry for Life Sciences,School of Life Sciences,Nanjing University,Nanjing 210023,China State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences,Nanjing University,Nanjing 210023,China
医药卫生
colitis-associated tumorigenesisepithelial-specific C/EBPβCXCL1/CXCL2/CXCL5-CXCR2 axisCXCR2-mediated neutrophil infiltration
《Acta Biochimica et Biophysica Sinica》 2026 (4)
P.882-894,13
supported by the grants from the National Natural Science Foundation of China(Nos.31771550,31870821 and 81972267)the Jiangsu Provincial Science and Technology Plan Special Fund(No.BM2023008).
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