Novel NOTCH-Binding Protein Directs Self-Renewal of Tumor-Initiating Stem-like Cells and HCC Development through Cell Fate Reprogramming

Liver tumor-initiating stem-like cells (TICs) which are defective in asymmetric cell division and responsible for liver tumor recurrence (PNAS 106, 1548-1553; Cell Metab 23, 206-219), have been isolated from 4 different animal models of HCC and patient HCC (J Clin Invest 2013;123:2832-49). We identified a novel NUMB binding protein, TBC1D15 in TICs, which is upregulated and destabilizes p53 via NUMB phosphorylation (p-NUMB) (Hepatology 62, 1466-1479). However, TBC1D15 still transforms p53-deficient hepatoblasts, suggesting other undisclosed mechanisms facilitated by this oncoprotein