Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer

Shuaishuai Teng, Yang Eric Li, Ming Yang, Rui Qi, Yiming Huang, Qianyu Wang, Yanmei Zhang, Shanwen Chen, Shasha Li, Kequan Lin, Yang Cao, Qunsheng Ji, Qingyang Gu, Yujing Cheng, Zai Chang, Wei Guo, Pengyuan Wang, Ivan Garcia-Bassets, Zhi John Lu, Dong Wang

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Metastasis, the development of secondary malignant growths at a distance from a primary tumor, is the cause of death for 90% of cancer patients, but little is known about how metastatic cancer cells adapt to and colonize new tissue environments. Here, using clinical samples, patient-derived xenograft (PDX) samples, PDX cells, and primary/metastatic cell lines, we discovered that liver metastatic colorectal cancer (CRC) cells lose their colon-specific gene transcription program yet gain a liver-specific gene transcription program. We showed that this transcription reprogramming is driven by a reshaped epigenetic landscape of both typical enhancers and super-enhancers. Further, we identified that the liver-specific transcription factors FOXA2 and HNF1A can bind to the gained enhancers and activate the liver-specific gene transcription, thereby driving CRC liver metastasis. Importantly, similar transcription reprogramming can be observed in multiple cancer types. Our data suggest that reprogrammed tissue-specific transcription promotes metastasis and should be targeted therapeutically.

Original languageEnglish
Pages (from-to)34-49
Number of pages16
JournalCell Research
Volume30
Issue number1
DOIs
StatePublished - Jan 1 2020

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