TY - JOUR
T1 - NOTCH signaling regulates asymmetric cell fate of fast- and slow-cycling colon cancer-initiating cells
AU - Srinivasan, Tara
AU - Walters, Jewell
AU - Bu, Pengcheng
AU - Than, Elaine Bich
AU - Tung, Kuei Ling
AU - Chen, Kai Yuan
AU - Panarelli, Nicole
AU - Milsom, Jeff
AU - Augenlicht, Leonard
AU - Lipkin, Steven M.
AU - Shen, Xiling
N1 - Publisher Copyright:
©2016 AACR.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84975029635&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84975029635&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-15-3198
DO - 10.1158/0008-5472.CAN-15-3198
M3 - Article
C2 - 27197180
AN - SCOPUS:84975029635
SN - 0008-5472
VL - 76
SP - 3411
EP - 3421
JO - Cancer Research
JF - Cancer Research
IS - 11
ER -
