Close
The page header's logo
About
FAQ
Home
Collections
Login
USC Login
Register
0
Selected 
Invert selection
Deselect all
Deselect all
 Click here to refresh results
 Click here to refresh results
USC
/
Digital Library
/
University of Southern California Dissertations and Theses
/
Cell fate reprogramming of liver tumor-initiating stem-like cells via phosphorylated NUMB and TBC1D15
(USC Thesis Other) 

Cell fate reprogramming of liver tumor-initiating stem-like cells via phosphorylated NUMB and TBC1D15

doctype icon
play button
PDF
 Download
 Share
 Open document
 Flip pages
 Download a page range
Contact Us
Contact Us
Copy asset link
Request this asset
Abstract (if available)
Abstract Tumor-initiating stem-like cells (TICs) give rise to diverse tumors and are responsible for chemotherapy/radiation resistance and tumor recurrence. Stem cell populations are maintained through asymmetric self-renewing divisions in which one daughter cell commits to a specific fate while the other retains the multipotent characteristics of its parent. The p53 interacting partner protein NUMB preserves this intrinsic cellular asymmetry and functions as a vital barrier against pluripotency and the unchecked expansion of TICs. The incidence of hepatocellular carcinoma (HCC) increases synergistically in alcoholic hepatitis C virus (HCV) patients, but the underlying mechanisms for this devastating complication are not yet understood. The central hypothesis is that accentuated TLR4-NANOG-mediated NUMB phosphorylation and TBC1D1 upregulation promote self-renewal of TICs and proteolysis of p53 in liver oncogenesis caused by HCV and alcohol. ❧ In this study, we determined the causal roles of NUMB phosphorylation and TBC1D15 in alcohol-induced liver tumorigenesis in HCV-Tg mice. Liver-specific overexpression of a non-phosphorylatable NUMB mutant, using tamoxifen-inducible Albumin-Cre-ERT2, prevents liver oncogenesis in alcohol-fed HCV transgenic mice. Liver-specific deletion of TBC1D15 attenuates loss of p53 and liver oncogenesis in alcohol-fed HCV-Tg mice by using the compound mice generated via crossing Ns5aTg with Alb-CreERT2 
Linked assets
University of Southern California Dissertations and Theses
doctype icon
University of Southern California Dissertations and Theses 
Action button
Conceptually similar
Targeting mitochondrion-nucleus PDH1 transfer to suppress self-renewal and epigenetic NANOG reprogramming of tumor-initiating cells
PDF
Targeting mitochondrion-nucleus PDH1 transfer to suppress self-renewal and epigenetic NANOG reprogramming of tumor-initiating cells 
Roles of epithelial-mesenchymal transition and niche in tumorigenesis of tumor-initiating cells
PDF
Roles of epithelial-mesenchymal transition and niche in tumorigenesis of tumor-initiating cells 
Identification of molecular mechanism for cell-fate decision in liver; &, SARS-CoV replicon inhibitor high throughput drug screening
PDF
Identification of molecular mechanism for cell-fate decision in liver; &, SARS-CoV replicon inhibitor high throughput drug screening 
Tri-specific T cell engager immunotherapy targeting tumor initiating cells
PDF
Tri-specific T cell engager immunotherapy targeting tumor initiating cells 
Polycomb repressive complex 2 subunit stabilizes NANOG to maintain self-renewal in hepatocellular carcinoma tumor-initiating stem-like cells
PDF
Polycomb repressive complex 2 subunit stabilizes NANOG to maintain self-renewal in hepatocellular carcinoma tumor-initiating stem-like cells 
PTEN deletion induced tumor initiating cells: Strategies to accelerate the disease progression of liver cancer
PDF
PTEN deletion induced tumor initiating cells: Strategies to accelerate the disease progression of liver cancer 
Tri-specific T cell engager immunotherapy targeting tumor initiating cells
PDF
Tri-specific T cell engager immunotherapy targeting tumor initiating cells 
Steatosis induces Wnt/β-catenin pathway to stimulate proliferation of hepatic tumor initiating cells and promote liver cancer development
PDF
Steatosis induces Wnt/β-catenin pathway to stimulate proliferation of hepatic tumor initiating cells and promote liver cancer development 
Mechanisms of nuclear translocation of pyruvate dehydrogenase and its effects on tumorigenesis of hepatocellular carcinoma…
PDF
Mechanisms of nuclear translocation of pyruvate dehydrogenase and its effects on tumorigenesis of hepatocellular carcinoma… 
Synergism between TLR4-c-JUN axis and surface receptor stimulation translocate c-MYC into Ig loci, through AID leading to lymphomagenesis
PDF
Synergism between TLR4-c-JUN axis and surface receptor stimulation translocate c-MYC into Ig loci, through AID leading to lymphomagenesis 
Functional characterization of a prostate cancer risk region
PDF
Functional characterization of a prostate cancer risk region 
Targeting glioma cancer stem cells for the treatment of glioblastoma multiforme
PDF
Targeting glioma cancer stem cells for the treatment of glioblastoma multiforme 
Lnc-RNA and WNT signal synergistically promotes self-renewal of tumor initiating stem-like cells via epigenetic regulation
PDF
Lnc-RNA and WNT signal synergistically promotes self-renewal of tumor initiating stem-like cells via epigenetic regulation 
Exploration of the roles of cancer stem cells and survivin in the pathogenesis and progression of prostate cancer
PDF
Exploration of the roles of cancer stem cells and survivin in the pathogenesis and progression of prostate cancer 
The effect of estradiol on TAZ in stromal cell line ST2 in osteoblast differentiation and ER+breast cancer cell
PDF
The effect of estradiol on TAZ in stromal cell line ST2 in osteoblast differentiation and ER+breast cancer cell 
Hepatic c-Jun overexpression metabolically reprograms cancer cells through mTORC2/AKT pathway
PDF
Hepatic c-Jun overexpression metabolically reprograms cancer cells through mTORC2/AKT pathway 
The role of endoplasmic reticulum chaperones in adipogenesis, liver cancer and mammary gland development
PDF
The role of endoplasmic reticulum chaperones in adipogenesis, liver cancer and mammary gland development 
Methodology of exploring the role of SOX9 in the human HCC stem-like cells
PDF
Methodology of exploring the role of SOX9 in the human HCC stem-like cells 
Identification and characterization of adult stem cells in the oral cavity
PDF
Identification and characterization of adult stem cells in the oral cavity 
Role of STAT3 phosphorylation in mouse embryonic stem cell self-renewal and differentiation
PDF
Role of STAT3 phosphorylation in mouse embryonic stem cell self-renewal and differentiation 
Action button
Asset Metadata
Creator Zheng, Mengmei (author) 
Core Title Cell fate reprogramming of liver tumor-initiating stem-like cells via phosphorylated NUMB and TBC1D15 
School Keck School of Medicine 
Degree Master of Science 
Degree Program Biochemistry and Molecular Biology 
Publication Date 01/30/2018 
Defense Date 11/14/2017 
Publisher University of Southern California (original), University of Southern California. Libraries (digital) 
Tag liver cancer,notch,Numb,OAI-PMH Harvest,TBC1D15 
Language English
Contributor Electronically uploaded by the author (provenance) 
Advisor Machida, Keigo (committee chair), Farnham, Peggy (committee member), Rice, Judd (committee member) 
Creator Email mengmeiz@usc.edu,morre.zheng@hotmail.com 
Permanent Link (DOI) https://doi.org/10.25549/usctheses-c40-465326 
Unique identifier UC11268518 
Identifier etd-ZhengMengm-5976.pdf (filename),usctheses-c40-465326 (legacy record id) 
Legacy Identifier etd-ZhengMengm-5976.pdf 
Dmrecord 465326 
Document Type Thesis 
Rights Zheng, Mengmei 
Type texts
Source University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection) 
Access Conditions The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law.  Electronic access is being provided by the USC Libraries in agreement with the a... 
Repository Name University of Southern California Digital Library
Repository Location USC Digital Library, University of Southern California, University Park Campus MC 2810, 3434 South Grand Avenue, 2nd Floor, Los Angeles, California 90089-2810, USA
Tags
liver cancer
notch
Numb
TBC1D15