title: A metabolic signature of colon cancer initiating cells.
abstract: Colon cancer initiating cells (CCICs) are more tumorigenic and metastatic than the majority of colorectal cancer (CRC) cells. CCICs have also been associated with stem cell-like properties. However, there is a lack of system-level understanding of what mechanisms distinguish CCICs from common CRC cells. We compared the transcriptomes of CD133+ CCICs and CD133- CRC cells from multiple sources, which identified a distinct metabolic signature for CD133(high) CCICs. High-resolution unbiased metabolomics was then performed to validate this CCIC metabolic signature. Specifically, levels of enzymes and metabolites involved in glycolysis, the citric acid (TCA) cycle, and cysteine and methionine metabolism are altered in CCICs. Analyses of the alterations further suggest an epigenetic link. This metabolic signature provides mechanistic insights into CCIC phenotypes and may serve as potential biomarkers and therapeutic targets for future CRC treatment.
authors.forename: Kai-Yuan
authors.initials: KY
authors.lastname: Chen
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Liu
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Bu
authors.forename: Chieh-Sheng
authors.initials: CS
authors.lastname: Lin
authors.forename: Nikolai
authors.initials: N
authors.lastname: Rakhilin
authors.forename: Jason W
authors.initials: JW
authors.lastname: Locasale
authors.forename: Xiling
authors.initials: X
authors.lastname: Shen
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D050260:Carbohydrate Metabolism; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D003545:Cysteine / Q000378:metabolism; D015536:Down-Regulation; D005787:Gene Frequency; D006019:Glycolysis; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D055442:Metabolome; D008715:Methionine / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D059467:Transcriptome
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D008715:Methionine; D003545:Cysteine