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Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer

ABSTRACT: Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer

PROVIDER: PRJNA418437 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6293150.fastq.gz	Fastqsanger.gz
	SRR6293160.fastq.gz	Fastqsanger.gz
	SRR6293151.fastq.gz	Fastqsanger.gz
	SRR6293161.fastq.gz	Fastqsanger.gz
	SRR6293162.fastq.gz	Fastqsanger.gz

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Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer (ChIP-Seq)

Project description:Metastasis is the cause of death for 90% of cancer patients, but little is known about how cancer cells adapt to and colonize new tissue environments. Using clinical samples and primary/metastatic cell lines, we found metastatic colorectal cancer (CRC) cells lose their colon-specific gene transcription program and gain a liver-specific gene transcription program as they metastasize in the liver. We revealed this transcription reprogramming is driven by a reshaped epigenetic landscape of both typical and super-enhancers. Further, we identified FOXA2, a liver-specific transcription factor, plays a key role in this transcription reprogramming and the colonization of metastatic CRC cells in the liver. Notably, this transcription reprogramming is also observed in multiple cancer types. Our data demonstrate that epigenetically reprogrammed tissue-specific transcription promotes metastasis and should be targeted therapeutically.

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Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer (RNA-Seq)

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

Project description: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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