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Full-Text Articles in Cell and Developmental Biology

Chronic Alcohol Exposure Induces Hepatocyte Damage By Inducing Oxidative Stress, Satb2 And Stem Cell-Like Characteristics, And Activating Lipogenesis, Wei Yu, Yiming Ma, Sushant K. Shrivastava, Rakesh K. Srivastava, Sharmila Shankar Apr 2022

Chronic Alcohol Exposure Induces Hepatocyte Damage By Inducing Oxidative Stress, Satb2 And Stem Cell-Like Characteristics, And Activating Lipogenesis, Wei Yu, Yiming Ma, Sushant K. Shrivastava, Rakesh K. Srivastava, Sharmila Shankar

School of Medicine Faculty Publications

Alcohol is a risk factor for hepatocellular carcinoma (HCC). However, the molecular mechanism by which chronic alcohol consumption contributes to HCC is not well understood. The purpose of the study was to demonstrate the effects of chronic ethanol exposure on the damage of human normal hepatocytes. Our data showed that chronic exposure of hepatocytes with ethanol induced changes similar to transformed hepatocytes that is, exhibited colonies and anchorage-independent growth. These damaged hepatocytes contained high levels of reactive oxygen species (ROS) and showed induction of the SATB2 gene. Furthermore, damaged hepatocytes gained the phenotypes of CSCs which expressed stem cell markers …


Rapid Cell Phenotyping Using Array-Based Sensors: Applications In Cancer Stem Cell Therapy And High-Content Screening, Yingying Geng Jun 2021

Rapid Cell Phenotyping Using Array-Based Sensors: Applications In Cancer Stem Cell Therapy And High-Content Screening, Yingying Geng

Doctoral Dissertations

Cell surface harbors rich information regarding the status of cell health. Being able to monitor and detect its changes in response to stimuli will provide crucial information in drug discovery, disease diagnosis, and human health. Despite the efforts and breakthroughs made possible through the specific sensing approach, there are significant challenges in extracting the information on the cell surface in a quantitative and reliable way. To address this challenge, I took the approach of array-based, hypothesis-free sensing in which the engineered sensors selectively interact with target analytes, producing a distinct pattern of response that enables analyte identification. This signature-based pattern …


Longitudinal Clonal Lineage Dynamics And Functional Characterization Of Pancreatic Cancer Chemo-Resistance And Metastasization, Chieh-Yuan Li Aug 2020

Longitudinal Clonal Lineage Dynamics And Functional Characterization Of Pancreatic Cancer Chemo-Resistance And Metastasization, Chieh-Yuan Li

Dissertations & Theses (Open Access)

In recent years, technological advancements, such as next-generation sequencing and single-cell interrogation techniques, have enriched our understanding in tumor heterogeneity. By dissecting tumors and characterizing clonal lineages, we are better understanding the intricacies of tumor evolution. Tumors are represented by the presence of and dynamic interactions amongst clonal lineages. Each lineage and each cell contributes to tumor dynamics through intrinsic and extrinsic mechanisms, and the variable responses of clones to perturbations in the environment, especially therapeutics, underlie disease progression and relapse. Thus, there exists a pressing need to understand the molecular mechanisms that determine the functional heterogeneity of tumor sub-clones …


Vegf/Neuropilin Signaling In Cancer Stem Cells, Arthur M. Mercurio Mar 2019

Vegf/Neuropilin Signaling In Cancer Stem Cells, Arthur M. Mercurio

Arthur M. Mercurio

The function of vascular endothelial growth factor (VEGF) in cancer extends beyond angiogenesis and vascular permeability. Specifically, VEGF-mediated signaling occurs in tumor cells and this signaling contributes to key aspects of tumorigenesis including the self-renewal and survival of cancer stem cells (CSCs). In addition to VEGF receptor tyrosine kinases, the neuropilins (NRPs) are critical for mediating the effects of VEGF on CSCs, primarily because of their ability to impact the function of growth factor receptors and integrins. VEGF/NRP signaling can regulate the expression and function of key molecules that have been implicated in CSC function including Rho family guanosine triphosphatases …


P4ha1 Is A New Regulator Of The Hif-1 Pathway In Breast Cancer, Ren Xu Jan 2019

P4ha1 Is A New Regulator Of The Hif-1 Pathway In Breast Cancer, Ren Xu

Markey Cancer Center Faculty Publications

Hypoxia-Inducible Factor (HIF)-1 is a transcription factor that plays the key role in response to low oxygen concentrations, or hypoxia. Activation of the HIF-1 pathway is not only crucial for normal tissue development and function, but also involved in disease progression, such as cancer. Cancer cells proliferate rapidly in solid tumors, and thus, solid tumors consume much more oxygen and nutrients than normal tissue and generate oxygen tension. It is well established that oxygen tension in solid tumor tissue induces the aberrant activation of the HIF-1 pathway, and subsequently promotes angiogenesis and tumor progression. Breast cancer is a heterogeneous disease …


Twist-Mediated Epithelial-Mesenchymal Transition Promotes Breast Tumor Cell Invasion Via Inhibition Of Hippo Pathway, Yifan Wang, Jingyi Liu, Xuhua Ying, Pengnian Charles Lin, Binhua P. Zhou Apr 2016

Twist-Mediated Epithelial-Mesenchymal Transition Promotes Breast Tumor Cell Invasion Via Inhibition Of Hippo Pathway, Yifan Wang, Jingyi Liu, Xuhua Ying, Pengnian Charles Lin, Binhua P. Zhou

Molecular and Cellular Biochemistry Faculty Publications

Twist is a key transcription factor for Epithelial-mesenchymal transition (EMT), which is a cellular de-differentiation program that promotes invasion and metastasis, confers tumor cells with cancer stem cell (CSC)-like characteristics, and increases therapeutic resistance. However, the mechanisms that facilitate the functions of Twist remain unclear. Here we report that Twist overexpression increased expression of PAR1, an upstream regulator of the Hippo pathway; PAR1 promotes invasion, migration, and CSC-like properties in breast cancer by activating the transcriptional co-activator TAZ. Our study indicates that Hippo pathway inhibition is required for the increased migratory and invasiveness ability of breast cancer cells in Twist-mediated …


The Chemopreventive Effect Of Polymethoxyflavones: Targeting The Colorectal Cancer Stem Cells, Fei Xu Nov 2015

The Chemopreventive Effect Of Polymethoxyflavones: Targeting The Colorectal Cancer Stem Cells, Fei Xu

Doctoral Dissertations

Among all the cancers, the death rate of colorectal cancer is one of the highest. Evidence from both murine xenograft model and human trials have shown cancer stem cells (CSCs) are responsible for the initiation, metastasis and recurrence of multiple cancers therefore targeting colorectal CSCs would be a promising chemo-preventive/ therapeutic strategy. Polymethoxyflavones including nobiletin (NBT) and 5-demethylatednobiletin (5DN) are exclusively found in citrus peels and have been shown to have anti-cancer effects. Our previous studies in the biotransformation and tissue distribution of NBT and 5DN have shown that in order to fuller evaluate the biological impact of those two …


Microrna Regulation Of Prostate Cancer Stem/Progenitor Cells And Prostate Cancer Development, Can Liu May 2012

Microrna Regulation Of Prostate Cancer Stem/Progenitor Cells And Prostate Cancer Development, Can Liu

Dissertations & Theses (Open Access)

Most human tumors contain a population of cells with stem cell properties, called cancer stem cells (CSCs), which are believed to be responsible for tumor establishment, metastasis, and resistance to clinical therapy. It’s crucial to understand the regulatory mechanisms unique to CSCs, so that we may design CSC-specific therapeutics. Recent discoveries of microRNA (miRNA) have provided a new avenue in understanding the regulatory mechanisms of cancer. However, how miRNAs may regulate CSCs is still poorly understood. Here, we present miRNA expression profiling in six populations of prostate cancer (PCa) stem/progenitor cells that possess distinct tumorigenic properties. Six miRNAs were identified …


Oncogenesis And Cancer Stem Cells: Current Opinions And Future Directions., Xiaoyu Cheng, Helen O'Neill Dec 2008

Oncogenesis And Cancer Stem Cells: Current Opinions And Future Directions., Xiaoyu Cheng, Helen O'Neill

Helen O'Neill

There is increasing evidence to show that only a subset of cancer cells drives the growth and progression of a tumour. These cells share similar properties with normal stem cells and are termed 'cancer stem cells'. Cancer stem cells have been identified in acute myeloid leukaemia and in some solid tumours by their distinct expression of cell surface antigens. Their long-term, self-renewing capacity is thought to be a determining factor in the maintenance and regrowth of the tumour. Studies on haematopoietic cancers show that important signalling pathways and genes for normal haematopoiesis, such as Wnt, NF-kappaB, Notch, hedgehog (Hh) and …