NOTCH Signaling Regulates Asymmetric Cell Fate of Fast- and Slow-Cycling Colon Cancer-Initiating Cells.

TitleNOTCH Signaling Regulates Asymmetric Cell Fate of Fast- and Slow-Cycling Colon Cancer-Initiating Cells.
Publication TypeJournal Article
Year of Publication2016
AuthorsSrinivasan, T, Walters, J, Bu, P, Than, EBich, Tung, K-L, Chen, K-Y, Panarelli, N, Milsom, J, Augenlicht, L, Lipkin, SM, Shen, X
JournalCancer Res
Volume76
Issue11
Pagination3411-21
Date Published2016 Jun 01
ISSN1538-7445
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.

DOI10.1158/0008-5472.CAN-15-3198
Alternate JournalCancer Res.
PubMed ID27197180
PubMed Central IDPMC4891252
Grant ListR01 GM095990 / GM / NIGMS NIH HHS / United States
R01 GM114254 / GM / NIGMS NIH HHS / United States
UL1 TR001414 / TR / NCATS NIH HHS / United States