TY - JOUR
T1 - Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer
AU - Teng, Shuaishuai
AU - Li, Yang Eric
AU - Yang, Ming
AU - Qi, Rui
AU - Huang, Yiming
AU - Wang, Qianyu
AU - Zhang, Yanmei
AU - Chen, Shanwen
AU - Li, Shasha
AU - Lin, Kequan
AU - Cao, Yang
AU - Ji, Qunsheng
AU - Gu, Qingyang
AU - Cheng, Yujing
AU - Chang, Zai
AU - Guo, Wei
AU - Wang, Pengyuan
AU - Garcia-Bassets, Ivan
AU - Lu, Zhi John
AU - Wang, Dong
N1 - Publisher Copyright:
© 2019, IBCB, SIBS, CAS.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85076423729&partnerID=8YFLogxK
U2 - 10.1038/s41422-019-0259-z
DO - 10.1038/s41422-019-0259-z
M3 - Article
C2 - 31811277
AN - SCOPUS:85076423729
SN - 1001-0602
VL - 30
SP - 34
EP - 49
JO - Cell Research
JF - Cell Research
IS - 1
ER -