Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer (RNA-Seq). Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer (RNA-Seq)

Metastasis is the cause of death for 90% of cancer patients, but little is known about how cancer cells adapt to and colonize new tissue environments. Using clinical samples and primary/metastatic cell lines, we found metastatic colorectal cancer (CRC) cells lose their colon-specific gene transcription program and gain a liver-specific gene transcription program as they metastasize in the liver. We revealed this transcription reprogramming is driven by a reshaped epigenetic landscape of both typical and super-enhancers. Further, we identified FOXA2, a liver-specific transcription factor, plays a key role in this transcription reprogramming and the colonization of metastatic CRC cells in the liver. Notably, this transcription reprogramming is also observed in multiple cancer types. Our data demonstrate that epigenetically reprogrammed tissue-specific transcription promotes metastasis and should be targeted therapeutically. Overall design: Examination of 4 different histone modifications and transcriptome in 2 cell lines.

转移是90%癌症患者的致死原因，但目前学界对癌细胞如何适应并定植于新组织微环境的机制仍知之甚少。本研究采用临床样本及原代、转移细胞系开展实验，发现转移性结直肠癌（colorectal cancer, CRC）细胞在肝脏发生转移定植时，会丢失结肠特异性基因转录程序，并获得肝脏特异性基因转录程序。本研究揭示，该转录重编程由典型增强子与超级增强子共同重塑的表观遗传景观所驱动。进一步研究发现，肝脏特异性转录因子FOXA2在该转录重编程过程以及转移性结直肠癌（CRC）细胞的肝脏定植中发挥关键作用。值得注意的是，这类转录重编程在多种癌症类型中均存在。本研究数据表明，经表观遗传重编程的组织特异性转录程序可促进肿瘤转移，因此可作为治疗靶点。实验设计概要：对2种细胞系中的4种不同组蛋白修饰及转录组进行检测分析。