Journal
CELL RESEARCH
Volume 30, Issue 1, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41422-019-0259-z
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Funding
- National Natural Science Foundation of China [81673460, 31771461, 81972798]
- Tsinghua-Peking Joint Center for Life Sciences
- Beijing Municipal Science & Technology Commission
- Fok YingTong Education Foundation
- Beijing Advanced Innovation Center for Structural Biology
- Bio-Computing Platform of Tsinghua University Branch of China National Center for Protein Sciences (Beijing)
- U.S. Department of Defense [W81XWH-14-1-0089, W81XWH-121-0358]
- Ovarian Cancer Research Fund Alliance (Liz Tilberis Award) bequest from the Estate of Agatha Pepper Fort
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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.
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