同源盒蛋白纳米
SOX2
胰腺癌
染色质免疫沉淀
癌症研究
癌症干细胞
CXCR4型
医学
干细胞
细胞生物学
癌症
转录因子
生物
内科学
化学
免疫学
诱导多能干细胞
胚胎干细胞
趋化因子
基因表达
免疫系统
基因
发起人
生物化学
作者
Tianxing Zhou,Jing Liu,Yongjie Xie,Shuai Yuan,Yu Guo,Weiwei Bai,Kaili Zhao,Wenna Jiang,Hongwei Wang,Haotian Wang,Tiansuo Zhao,Chongbiao Huang,Song Gao,Xiuchao Wang,Shengyu Yang,Jihui Hao
出处
期刊:Gut
[BMJ]
日期:2021-03-05
卷期号:71 (2): 357-371
被引量:25
标识
DOI:10.1136/gutjnl-2020-321952
摘要
The crosstalk between cancer stem cells (CSCs) and their niche is required for the maintenance of stem cell-like phenotypes of CSCs. Here, we identified E26 transformation-specific homologous factor (EHF) as a key molecule in decreasing the sensitivity of pancreatic cancer (PC) cells to CSCs' niche stimulus. We also explored a therapeutic strategy to restore the expression of EHF.We used a LSL-KrasG12D/+mice, LSL-Trp53R172H/+ and Pdx1-Cre (KPC) mouse model and samples from patients with PC. Immunostaining, flow cytometry, sphere formation assays, anchorage-independent growth assay, in vivo tumourigenicity, reverse transcription PCR, chromatin immunoprecipitation (ChIP) and luciferase analyses were conducted in this study.CXCL12 derived from pancreatic stellate cells (PSCs) mediates the crosstalk between PC cells and PSCs to promote PC stemness. Tumorous EHF suppressed CSC stemness by decreasing the sensitivity of PC to CXCL12 stimulus and inhibiting the crosstalk between PC and CSC-supportive niches. Mechanically, EHF suppressed the transcription of the CXCL12 receptor CXCR4. EHF had a cell autonomous role in suppressing cancer stemness by inhibiting the transcription of Sox9, Sox2, Oct4 and Nanog. Rosiglitazone suppressed PC stemness and inhibited the crosstalk between PC and PSCs by upregulating EHF. Preclinical KPC mouse cohorts demonstrated that rosiglitazone sensitised PDAC to gemcitabine therapy.EHF decreased the sensitivity of PC to the stimulus from PSC-derived CSC-supportive niche by negatively regulating tumorous CXCR4. Rosiglitazone could be used to target PC stem cells and the crosstalk between CSCs and their niche by upregulating EHF.
科研通智能强力驱动
Strongly Powered by AbleSci AI