Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer
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摘要:
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 obsenved in multiple cancer types.Our data suggest that reprogrammed tissue-specific transcription promotes metastasis and should be targeted therapeutically.