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

摘要

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-cycling 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, relying on MYC for their proliferation, whereas slow-cycling CCIC express markers such as BMI1 and hTERT and 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-cycling and fast-cycling CCIC.