Regenerative origin of metastasis stem cells

UID: 10505

Author(s): Ganesh, Karuna*, Massagué, Joan*, Koche, Richard Patrick*, Reuter, Vincent Patrick* * MSK affiliated

Description: Author summary from Gene Expression Omnibus: "Assaying binding of REST to DNA with ChIP-seq reveals the role of REST in transcriptional regulation in colorectal cancer (CRC) metastatic stem cells (MetSCs). REST is especially relevant to regulation of L1CAM expression."

Overall Design: "ChIP-seq of binding of REST to DNA."

Abstract summary: "Metastasis-initiating cells with stem-like properties drive cancer lethality, yet their origins and relationship to primary-tumor-initiating stem cells are not known. We show that L1CAM+ cells in human colorectal cancer (CRC) have metastasis-initiating capacity, and we define their relationship to tissue regeneration. L1CAM is not expressed in the homeostatic intestinal epithelium, but is induced and required for epithelial regeneration following colitis and in CRC organoid growth. By using human tissues and mouse models, we show that L1CAM is dispensable for adenoma initiation but required for orthotopic carcinoma propagation, liver metastatic colonization and chemoresistance. L1CAMhigh cells partially overlap with LGR5high stem-like cells in human CRC organoids. Disruption of intercellular epithelial contacts causes E-cadherin–REST transcriptional derepression of L1CAM, switching chemoresistant CRC progenitors from an L1CAMlow to an L1CAMhigh state. Thus, L1CAM dependency emerges in regenerative intestinal cells when epithelial integrity is lost, a phenotype of wound healing deployed in metastasis-initiating cells."

Subject of Study

Subject(s)

OncoTree Cancer Type(s)

Bowel

Access via GEO

Accession #: GSE112555

Access via SRA
ChIP Sequence reads for 10 samples.
Accession #: SRP136835

Access via BioProject
Additional information about overall initiative.
Accession #: PRJNA448173
Access Restrictions: Free to All
Access Instructions: The NCBI Gene Expression Omnibus database provides open access to these files.
Associated Publications: Ganesh K, Basnet H, Kaygusuz Y, et al. L1CAM defines the regenerative origin of metastasis initiating cells in colorectal cancer. Cancer Research. 2020; 80(11 Suppl.):40.
Data Type: Genomic
Equipment Used: Illumina HiSeq 4000
High throughput gene sequencing system
Dataset Format(s): SRA, TAR, BIGWIG
Dataset Size: 6.0 GB (TAR of BIGWIG), 16.5 GB (SRA)

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