American Association for Cancer Research
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Supplementary Methods from NOTCH Signaling Regulates Asymmetric Cell Fate of Fast- and Slow-Cycling Colon Cancer–Initiating Cells

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posted on 2023-03-31, 00:13 authored by Tara Srinivasan, Jewell Walters, Pengcheng Bu, Elaine Bich Than, Kuei-Ling Tung, Kai-Yuan Chen, Nicole Panarelli, Jeff Milsom, Leonard Augenlicht, Steven M. Lipkin, Xiling Shen

Contains information about antibodies used for immunofluorescence and Western blotting and primers for RT-PCR.

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ARTICLE 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.

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