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Published October 2018 | public
Journal Article

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.

Additional Information

© 2018 by the American Association for the Study of Liver Diseases. Issue Online: 01 October 2018. This project was supported by NIH grants 1R01AA018857-01, pilot project funding (5P30DK048522-13), P50AA011999 (Animal Core, Morphology Core, and Pilot Project Program), P30CA014089 and R24AA012885 (Integrative Liver Cell Core). This research is also supported by a Research Scholar Grant, RSG-12-177-01-MPC and pilot funding (IRG-58-007-48) from the American Cancer Society. Disclosures: Hidekazu Tsukamoto – Gilead Sciences Inc.: Grant/Research Support; EA Pharma Co. Ltd: Consulting; Otsuka Pharmaceutical: Grant/Research Support. The following people have nothing to disclose: Ahmed Rokan, Vasu Punj, Linda S. Sher. Disclosure information not available at the time of publication: Hifzur Siddique, Mengmei Zheng, Yi Kou, Chia-Lin Chen Chen, Dinesh Babu Uthaya Kumar, Peleg Winer, Stanley M Tahara, Ratna Ray, Michael Elowitz, Chengyu Liang, Lin Chen, Keigo Machida

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August 19, 2023
October 18, 2023