title: NOTCH Signaling Regulates Asymmetric Cell Fate of Fast- and Slow-Cycling Colon Cancer-Initiating Cells.
abstract: Colorectal cancer cells with stem-like properties, referred to as colon cancer-initiating cells (CCIC), have high tumorigenic potential. While CCIC can differentiate to promote cellular heterogeneity, it remains unclear whether CCIC within a tumor contain distinct subpopulations. Here, we describe the co-existence of fast- and slow-cycling CCIC, which can undergo asymmetric division to generate each other, highlighting CCIC plasticity and interconvertibility. Fast-cycling CCIC express markers, such as LGR5 and CD133, rely on MYC for their proliferation, whereas slow-cycling CCIC express markers, such as BMI1 and hTERT, are independent of MYC. NOTCH signaling promotes asymmetric cell fate, regulating the balance between these two populations. Overall, our results illuminate the basis for CCIC heterogeneity and plasticity by defining a direct interconversion mechanism between slow- and fast-cycling CCIC. Cancer Res; 76(11); 3411-21. ©2016 AACR.
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York.
authors.forename: Tara
authors.initials: T
authors.lastname: Srinivasan
authors.affiliation: Departments of Medicine, Genetic Medicine Surgery and Pathology, Weill Cornell Medical College, New York, New York.
authors.forename: Jewell
authors.initials: J
authors.lastname: Walters
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York. School of Electrical and Computer Engineering, Cornell University, Ithaca, New York.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Bu
authors.affiliation: Departments of Medicine, Genetic Medicine Surgery and Pathology, Weill Cornell Medical College, New York, New York.
authors.forename: Elaine Bich
authors.initials: EB
authors.lastname: Than
authors.affiliation: Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York.
authors.forename: Kuei-Ling
authors.initials: KL
authors.lastname: Tung
authors.affiliation: School of Electrical and Computer Engineering, Cornell University, Ithaca, New York.
authors.forename: Kai-Yuan
authors.initials: KY
authors.lastname: Chen
authors.affiliation: Departments of Medicine, Genetic Medicine Surgery and Pathology, Weill Cornell Medical College, New York, New York.
authors.forename: Nicole
authors.initials: N
authors.lastname: Panarelli
authors.affiliation: Departments of Medicine, Genetic Medicine Surgery and Pathology, Weill Cornell Medical College, New York, New York.
authors.forename: Jeff
authors.initials: J
authors.lastname: Milsom
authors.affiliation: Medicine and Cell Biology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Leonard
authors.initials: L
authors.lastname: Augenlicht
authors.affiliation: Departments of Medicine, Genetic Medicine Surgery and Pathology, Weill Cornell Medical College, New York, New York. xs37@duke.edu stl2012@med.cornell.edu.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Lipkin
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York. School of Electrical and Computer Engineering, Cornell University, Ithaca, New York. Department of Biomedical Engineering, Duke University, Durham, North Carolina. xs37@duke.edu stl2012@med.cornell.edu.
authors.forename: Xiling
authors.initials: X
authors.lastname: Shen
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D019098:Telomerase / Q000378:metabolism; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; C116884:LGR5 protein, human; D043562:Receptors, G-Protein-Coupled; D051880:Receptors, Notch; D063150:Polycomb Repressive Complex 1; C509186:TERT protein, human; D019098:Telomerase