Title | NOTCH Signaling Regulates Asymmetric Cell Fate of Fast- and Slow-Cycling Colon Cancer-Initiating Cells. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Srinivasan, T, Walters, J, Bu, P, Than, EBich, Tung, K-L, Chen, K-Y, Panarelli, N, Milsom, J, Augenlicht, L, Lipkin, SM, Shen, X |
Journal | Cancer Res |
Volume | 76 |
Issue | 11 |
Pagination | 3411-21 |
Date Published | 2016 Jun 01 |
ISSN | 1538-7445 |
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. |
DOI | 10.1158/0008-5472.CAN-15-3198 |
Alternate Journal | Cancer Res. |
PubMed ID | 27197180 |
PubMed Central ID | PMC4891252 |
Grant List | R01 GM095990 / GM / NIGMS NIH HHS / United States R01 GM114254 / GM / NIGMS NIH HHS / United States UL1 TR001414 / TR / NCATS NIH HHS / United States |