Reconstruction of tissue-specific genome-scale metabolic models for human cancer stem cells

AbstractIt has been postulated that cancer stem cells (CSCs) are involved in all aspects of human cancer, although the mechanisms governing the regulation of CSC self-renewal in the cancer state remain poorly defined. In the literature, both the pro- and anti-oncogenic activities of autophagy have been demonstrated and are context-dependent. Mounting evidence has shown augmentation of CSC stemness by autophagy, yet mechanistic characterization and understanding are lacking. In the present study, by generating stable human lung CSC cell lines with the wild-type TP53 (A549), as well as cell lines in which TP53 was deleted (H1229), we show, for the first time, that autophagy augments the stemness of lung CSCs by degrading ubiquitinated p53. Furthermore, Zeb1 is required for TP53 regulation of CSC self-renewal. Moreover, TCGA data mining and analysis show that Atg5 and Zeb1 are poor prognostic markers of lung cancer. In summary, this study has elucidated a new CSC-based mechanism underlying the oncogenic activity of autophagy and the tumor suppressor activity of p53 in cancer, i.e., CSCs can exploit the autophagy-p53-Zeb1 axis for self-renewal, oncogenesis, and progression.

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Salinomycin as a Drug for Targeting Human Cancer Stem Cells

Journal of Biomedicine and Biotechnology ◽

10.1155/2012/950658 ◽

2012 ◽

Vol 2012 ◽

pp. 1-17 ◽

Cited By ~ 178

Author(s):

Cord Naujokat ◽

Roman Steinhart

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Epithelial Mesenchymal Transition ◽

Human Cancer ◽

Drug Transporters ◽

Molecular Complexes ◽

Cancer Therapies ◽

Mesenchymal Transition ◽

Heavily Pretreated ◽

Preclinical Trials

Cancer stem cells (CSCs) represent a subpopulation of tumor cells that possess self-renewal and tumor initiation capacity and the ability to give rise to the heterogenous lineages of malignant cells that comprise a tumor. CSCs possess multiple intrinsic mechanisms of resistance to chemotherapeutic drugs, novel tumor-targeted drugs, and radiation therapy, allowing them to survive standard cancer therapies and to initiate tumor recurrence and metastasis. Various molecular complexes and pathways that confer resistance and survival of CSCs, including expression of ATP-binding cassette (ABC) drug transporters, activation of the Wnt/β-catenin, Hedgehog, Notch and PI3K/Akt/mTOR signaling pathways, and acquisition of epithelial-mesenchymal transition (EMT), have been identified recently. Salinomycin, a polyether ionophore antibiotic isolated fromStreptomyces albus, has been shown to kill CSCs in different types of human cancers, most likely by interfering with ABC drug transporters, the Wnt/β-catenin signaling pathway, and other CSC pathways. Promising results from preclinical trials in human xenograft mice and a few clinical pilote studies reveal that salinomycin is able to effectively eliminate CSCs and to induce partial clinical regression of heavily pretreated and therapy-resistant cancers. The ability of salinomycin to kill both CSCs and therapy-resistant cancer cells may define the compound as a novel and an effective anticancer drug.

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Characterization of Gene Expression Patterns among Artificially Developed Cancer Stem Cells Using Spherical Self-Organizing Map

Cancer Informatics ◽

10.4137/cin.s39839 ◽

2016 ◽

Vol 15 ◽

pp. CIN.S39839 ◽

Cited By ~ 13

Author(s):

Akimasa Seno ◽

Tomonari Kasai ◽

Masashi Ikeda ◽

Arun Vaidyanath ◽

Junko Masuda ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Cancer Stem Cells ◽

Human Cancer ◽

Expression Patterns ◽

Embryonic Stem ◽

Culture Conditions ◽

Self Organizing Map ◽

Cancer Tissues ◽

Self Organizing

We performed gene expression microarray analysis coupled with spherical self-organizing map (sSOM) for artificially developed cancer stem cells (CSCs). The CSCs were developed from human induced pluripotent stem cells (hiPSCs) with the conditioned media of cancer cell lines, whereas the CSCs were induced from primary cell culture of human cancer tissues with defined factors ( OCT3/4, SOX2, and KLF4). These cells commonly expressed human embryonic stem cell (hESC)/hiPSC-specific genes ( POU5F1, SOX2, NANOG, LIN28, and SALL4) at a level equivalent to those of control hiPSC 201B7. The sSOM with unsupervised method demonstrated that the CSCs could be divided into three groups based on their culture conditions and original cancer tissues. Furthermore, with supervised method, sSOM nominated TMED9, RNASE1, NGFR, ST3GAL1, TNS4, BTG2, SLC16A3, CD177, CES1, GDF15, STMN2, FAM20A, NPPB, CD99, MYL7, PRSS23, AHNAK, and LOC152573 genes commonly upregulating among the CSCs compared to hiPSC, suggesting the gene signature of the CSCs.

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Abstract 3383: Expression and role of BORIS/CTCFL in human cancer stem cells

10.1158/1538-7445.am2012-3383 ◽

2012 ◽

Author(s):

Jean Benhattar ◽

Loredana Alberti

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Human Cancer

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Shrimp miRNA suppresses the stemness of human cancer stem cells via the PIN1 pathway

The FASEB Journal ◽

10.1096/fj.201900395rr ◽

2019 ◽

Vol 33 (10) ◽

pp. 10767-10779 ◽

Cited By ~ 3

Author(s):

Siyuan Zhang ◽

Xiaobo Zhang

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Human Cancer

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Preclinical drug metabolism and pharmacokinetics of salinomycin, a potential candidate for targeting human cancer stem cells

Chemico-Biological Interactions ◽

10.1016/j.cbi.2015.08.007 ◽

2015 ◽

Vol 240 ◽

pp. 146-152 ◽

Cited By ~ 10

Author(s):

Kahkashan Resham ◽

Prinesh N. Patel ◽

Dinesh Thummuri ◽

Lalita Guntuku ◽

Vanya Shah ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Drug Metabolism ◽

Human Cancer ◽

Potential Candidate

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Endothelial Interleukin-6 Defines the Tumorigenic Potential of Primary Human Cancer Stem Cells

Stem Cells ◽

10.1002/stem.1793 ◽

2014 ◽

Vol 32 (11) ◽

pp. 2845-2857 ◽

Cited By ~ 52

Author(s):

Sudha Krishnamurthy ◽

Kristy A. Warner ◽

Zhihong Dong ◽

Atsushi Imai ◽

Carolina Nör ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Interleukin 6 ◽

Human Cancer ◽

Tumorigenic Potential

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Gastric Cancer Stem Cells

Journal of Clinical Oncology ◽

10.1200/jco.2007.15.2603 ◽

2008 ◽

Vol 26 (17) ◽

pp. 2876-2882 ◽

Cited By ~ 123

Author(s):

Shigeo Takaishi ◽

Tomoyuki Okumura ◽

Timothy C. Wang

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Cancer Stem Cell ◽

Cell Biology ◽

Cancer Biology ◽

Human Cancer ◽

Immunodeficient Mice

Cancer stem cells are defined as the unique subpopulation in the tumors that possess the ability to initiate tumor growth and sustain self-renewal as well as metastatic potential. Accumulating evidence in recent years strongly indicate the existence of cancer stem cells in solid tumors of a wide variety of organs. In this review, we will discuss the possible existence of a gastric cancer stem cell. Our recent data suggest that a subpopulation with a defined marker shows spheroid colony formation in serum-free media in vitro, as well as tumorigenic ability in immunodeficient mice in vivo. We will also discuss the possible origins of the gastric cancer stem cell from an organ-specific stem cell versus a recently recognized new candidate bone marrow–derived cell (BMDC). We have previously shown that BMDC contributed to malignant epithelial cells in the mouse model of Helicobacter-associated gastric cancer. On the basis of these findings from animal model, we propose that a similar phenomenon may also occur in human cancer biology, particularly in the cancer origin of other inflammation-associated cancers. The expanding research field of cancer stem-cell biology may offer a novel clinical apparatus to the diagnosis and treatment of cancer.

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