CYP1B1 promotes colorectal cancer liver metastasis by enhancing the growth of metastatic cancer cells via a fatty acids-dependent manner

作者：Lei Jin, Ju Huang, Lei Guo, Bo Zhang, Qin Li, Hui Li, Mincheng Yu, Peiyi Xie, Qiang Yu, Zheng Chen, Shuang Liu, Yongfeng Xu, Yong‐Sheng Xiao, Ming Lu, Qing‐Hai Ye · 发表于：Journal of Gastrointestinal Oncology · 年份：2023 · DOI：10.21037/jgo-23-895 · 被引用次数：13 · 研究领域：Cancer, Lipids, and Metabolism、Cancer Cells and Metastasis、Cancer, Hypoxia, and Metabolism

Background: Liver metastasis (LM) accounts for most colorectal cancer (CRC)-related deaths. However, how metastatic CRC cells gain the ability to survive and grow in liver remains largely unknown. Methods: First, we screened differentially expressed genes (DEGs) between LM and paired primary tumors (PTs) in Gene Expression Omnibus (GEO) database, and identified cytochrome P450 1B1 (CYP1B1) as the only common differential gene. Then, we verified messenger RNA (mRNA) and protein expression level in clinical specimens. After constructing stable up-regulated CYP1B1 versions of HCT116 and RKO CRC cells and stable down-regulated CYP1B1 versions of SW480 and HT29 CRC cells, cell proliferation assays, subcutaneous tumor formation, and mouse LM models were used to comprehend its function. Next, we used RNA-seq to uncover specific mechanisms of growth; cell cycle, polymerase chain reaction (PCR), western blot (WB) and GEO series (GSE) datasets were used to verify its mechanism. Last, gas chromatography tandem mass spectrometry (GC-MS/MS) was adopted to examine which fatty acids were changed. Results: A significantly higher level of CYP1B1 was found in LM than in PT in paired clinical CRC LM samples (P<0.05). After CYP1B1 overexpression in HCT116 and RKO cells, cell proliferation abilities in vitro and in vivo were enhanced; LM of NOD.Cg-PrkdcscidIl2rgem1Smoc (NSG) mice were enhanced. And knockdown of CYP1B1 in SW480 and HT29 cells, cell proliferation abilities in vitro and in vivo were...