L1CAM defines the regenerative origin of metastasis-initiating cells in colorectal cancer.

ABSTRACT: 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. L1CAM^high cells partially overlap with LGR5^high stem-like cells in human CRC org

SUBMITTER: Ganesh K 

PROVIDER: S-EPMC7351134 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature