Format

Send to

Choose Destination
Cell Res. 2020 Jan;30(1):34-49. doi: 10.1038/s41422-019-0259-z. Epub 2019 Dec 6.

Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer.

Author information

1
MOE Key Lab of Bioinformatics, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China.
2
MOE Key Lab of Bioinformatics, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing, China.
3
Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
4
PKU-THU Center for Life Sciences, Tsinghua University, Beijing, China.
5
Division of General Surgery, Peking University First Hospital, Peking University, Beijing, China.
6
WuXi AppTec (Shanghai) Co., Ltd., Shanghai, 200131, China.
7
Zhejiang University-University of Edinburgh Institute, Haining, China.
8
School of Medicine, University of California, San Diego, La Jolla, CA, USA.
9
MOE Key Lab of Bioinformatics, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing, China. zhilu@tsinghua.edu.cn.
10
MOE Key Lab of Bioinformatics, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China. dwang@cdutcm.edu.cn.
11
Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China. dwang@cdutcm.edu.cn.
12
School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. dwang@cdutcm.edu.cn.

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.

PMID:
31811277
PMCID:
PMC6951341
[Available on 2021-01-01]
DOI:
10.1038/s41422-019-0259-z

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center