Evidence map›Paper›PMID 32555153›Full record

ArticleNature communications2020

p53 destabilizing protein skews asymmetric division and enhances NOTCH activation to direct self-renewal of TICs.

Hye Yeon Choi, Hifzur R Siddique, Mengmei Zheng, Yi Kou, Da-Wei Yeh, Tatsuya Machida, Chia-Lin Chen, Dinesh Babu Uthaya Kumar, Vasu Punj, Peleg Winer and 8 more

RetractedOpen access · goldAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.0field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. Asymmetric division of stem cells and its cancer relevance.Cell regeneration (London, England) · 2024
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Asymmetric Cell Division and Tumor Heterogeneity.Frontiers in cell and developmental biology · 2022
    Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 2 institutions in 2 countries.

Hye Yeon Choi *Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA, 90033, USA.
Hifzur R Siddique *Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA, 90033, USA.
Mengmei ZhengDepartment of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA, 90033, USA.
Yi KouDepartment of Chemistry and Biological Sciences, University of Southern California, Los Angeles, CA, 90089, USA.
Da-Wei YehDepartment of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA, 90033, USA.ORCID http://orcid.org/0000-0001-5637-7315
Tatsuya MachidaDepartment of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA, 90033, USA.
Chia-Lin ChenDepartment of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA, 90033, USA.
Dinesh Babu Uthaya KumarDepartment of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA, 90033, USA.ORCID http://orcid.org/0000-0001-7210-5811
Vasu PunjDepartment of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Peleg WinerDepartment of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA, 90033, USA.
Alejandro PitaDepartment of Surgery, University of Southern California, Los Angeles, CA, 90033, USA.
Linda SherDepartment of Surgery, University of Southern California, Los Angeles, CA, 90033, USA.
Stanley M TaharaDepartment of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA, 90033, USA.ORCID http://orcid.org/0000-0001-5097-0927
Ratna B RaySaint Louis University, St. Louis, MO, 63103, USA.
Chengyu LiangDepartment of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA, 90033, USA.ORCID http://orcid.org/0000-0001-6082-2143
Lin ChenDepartment of Chemistry and Biological Sciences, University of Southern California, Los Angeles, CA, 90089, USA.
Hidekazu TsukamotoDepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Keigo MachidaDepartment of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA, 90033, USA. keigo.machida@med.usc.edu.ORCID http://orcid.org/0000-0002-9721-8553
University of Southern California · USSaint Louis University · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4M
The Southernearch Center for ALPD and CirrhosisP50AA011999 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ANNA S. GUKOVSKAYA · 1999 to 2026
$45.8M
USC RESEARCH CENTER FOR LIVER DISEASES: PILOT PROGRAMSP30DK048522 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI OOKHTENS, MURAD · 1995 to 2020
$21.8M
NON-PARENCHYMAL LIVER CELL CORER24AA012885 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TSUKAMOTO, HIDEKAZU · 2001 to 2025
$8.1M
NANOG-positive cancer stem cells in liver oncogenesis induced by alcohol and HCVR01AA025204 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MACHIDA, KEIGO · 2017 to 2021
$1.9M
Nanog-positive cancer stem cells in and liver oncogenesis by alcohol and HCVR01AA018857 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MACHIDA, KEIGO · 2009 to 2013
$1.8M
Ultra-High Resolution CT Specimen Scanner for In Vitro ApplicationsS10RR027665 · NCRR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CONTI, PETER STEPHEN · 2010 to 2010
$492k
LncRNA with MSI2 and super-enhancer in liver cancer stem cells induced by alcoholR21AA025470 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MACHIDA, KEIGO · 2018 to 2019
$444k
IVIS Spectrum Optical Imaging Core ResourceS10OD021785 · OD · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CONTI, PETER STEPHEN · 2017 to 2017
$408k
Micro Computerized Tomography Imaging SystemS10RR019253 · NCRR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CONTI, PETER S · 2004 to 2004
$378k
NCI NIH HHS P30 CA014089NCRR NIH HHS S10 RR019253NCRR NIH HHS S10 RR027665NIAAA NIH HHS P50 AA011999NIAAA NIH HHS R01 AA018857NIAAA NIH HHS R01 AA025204NIAAA NIH HHS R21 AA025470NIAAA NIH HHS R24 AA012885NIDDK NIH HHS P30 DK048522NIH HHS S10 OD021785
6 · The paper itself

Abstract

Tumor-initiating stem-like cells (TICs) are defective in maintaining asymmetric cell division and responsible for tumor recurrence. Cell-fate-determinant molecule NUMB-interacting protein (TBC1D15) is overexpressed and contributes to p53 degradation in TICs. Here we identify TBC1D15-mediated oncogenic mechanisms and tested the tumorigenic roles of TBC1D15 in vivo. We examined hepatocellular carcinoma (HCC) development in alcohol Western diet-fed hepatitis C virus NS5A Tg mice with hepatocyte-specific TBC1D15 deficiency or expression of non-phosphorylatable NUMB mutations. Liver-specific TBC1D15 deficiency or non-p-NUMB expression reduced TIC numbers and HCC development. TBC1D15-NuMA1 association impaired asymmetric division machinery by hijacking NuMA from LGN binding, thereby favoring TIC self-renewal. TBC1D15-NOTCH1 interaction activated and stabilized NOTCH1 which upregulated transcription of NANOG essential for TIC expansion. TBC1D15 activated three novel oncogenic pathways to promote self-renewal, p53 loss, and Nanog transcription in TICs. Thus, this central regulator could serve as a potential therapeutic target for treatment of HCC.

Indexed as

AdultAgedAnimalsCarcinogenesisCarcinoma, HepatocellularCell DivisionCell Line, TumorFluorescence Resonance Energy TransferGTPase-Activating ProteinsHepacivirusHepatocytesHumansLiverLiver NeoplasmsMiceMiddle AgedGTPase-Activating ProteinsNOTCH1 protein, humanReceptor, Notch1Receptors, NotchTBC1D15 protein, humanTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID32555153
PMCPMC7299990
OpenAlexW3036121967

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.