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

Siddique, Hifzur and Zheng, Mengmei and Kou, Yi and Chen, Chia-Lin Chen and Kumar, Dinesh Babu Uthaya and Winer, Peleg and Rokan, Ahmed and Punj, Vasu and Sher, Linda S. and Tahara, Stanley M. and Ray, Ratna and Elowitz, Michael and Liang, Chengyu and Chen, Lin and Tsukamoto, Hidekazu and Machida, Keigo (2018) Novel NOTCH-Binding Protein Directs Self-Renewal of Tumor-Initiating Stem-like Cells and HCC Development through Cell Fate Reprogramming. Hepatology, 68 (S1). Art. No. 1365. ISSN 0270-9139.

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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.

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Elowitz, Michael0000-0002-1221-0967
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
Funding AgencyGrant Number
American Cancer SocietyRSG-12-177-01-MPC
American Cancer SocietyIRG-58-007-48
Issue or Number:S1
Record Number:CaltechAUTHORS:20181024-102930532
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Official Citation:(2018), Posters (Abstracts 301–2389). Hepatology, 68: 184-1353. doi:10.1002/hep.30257
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90393
Deposited By: Tony Diaz
Deposited On:24 Oct 2018 17:57
Last Modified:03 Oct 2019 20:24

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