转移
癌症研究
转录组
结直肠癌
上皮-间质转换
转录因子
细胞迁移
细胞
医学
血管生成
生物
癌症
病理
内科学
基因表达
基因
遗传学
生物化学
作者
Sheng Yang,Dongsheng Zhang,Qingyang Sun,Hongxu Nie,Yue Zhang,Xiaowei Wang,Yuanjian Huang,Yueming Sun
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2024-04-24
被引量:2
标识
DOI:10.1158/0008-5472.can-23-3264
摘要
Abstract Colorectal cancer (CRC) is one of the most common malignant tumors in humans, with liver metastasis being the primary cause of mortality. The epithelial-mesenchymal transition (EMT) process endows cancer cells with enhanced metastatic potential. To elucidate the cellular mechanisms driving EMT in CRC, we analyzed single-cell RNA-sequencing (scRNA-seq) data from 11 non-metastatic primary tumors (TnM) and 11 metastatic primary tumors (TM) from CRC patients. Compared to TnM group, the TM samples showed elevated numbers of malignant epithelial cell and cancer-associated fibroblast (CAF) subsets that displayed enrichments of EMT, angiogenesis, and TGF-β signaling pathways. One specific TM-enriched subgroup of malignant epithelial cells underwent EMT to trans-differentiate into CXCL1+ CAFs that subsequently differentiated into SFRP2+ CAFs, which was validated by spatial transcriptomic and pseudotime trajectory analyses. Furthermore, cell-cell communication analysis identified BHLHE40 as a probable key transcription factor driving EMT that was associated with poor prognosis. Finally, in vitro and in vivo experiments functionally substantiated that BHLHE40 promoted the proliferation, invasion, migration, EMT, and liver metastasis of CRC cells. In summary, this study identified BHLHE40 as a key transcription factor regulating EMT that promotes liver metastasis in CRC.
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