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Aldehyde dehydrogenase: Its role as a cancer stem cell marker comes down to the specific isoform

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TLDR
The suggested roles of ALDH in CSC biology and the immunohistological studies testing the potential application of AL DH isoforms as novel cancer prognostic indicators are reviewed.
Abstract
Recent evidence suggests that enhanced aldehyde dehydrogenase (ALDH) activity is a hallmark of cancer stem cells (CSC) measurable by the aldefluor assay. ALDH1A1, one of 19 ALDH isoforms expressed in humans, was generally believed to be responsible for the ALDH activity of CSCs. More recently, experiments with murine hematopoietic stem cells, murine progenitor pancreatic cells, and human breast CSCs indicate that other ALDH isoforms, particularly ALDH1A3, significantly contribute to aldefluor positivity, which may be tissue and cancer specific. Therefore, potential prognostic application involving the use of CSC prevalence in tumor tissue to predict patient outcome requires the identification and quantification of specific ALDH isoforms. Herein we review the suggested roles of ALDH in CSC biology and the immunohistological studies testing the potential application of ALDH isoforms as novel cancer prognostic indicators.

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Mesenchymal glioma stem cells are maintained by activated glycolytic metabolism involving aldehyde dehydrogenase 1A3.

TL;DR: Two mutually exclusive GSC subtypes, harboring distinct metabolic signaling pathways, represent intertumoral glioma heterogeneity and highlight previously unidentified roles of ALDH1A3-associated signaling that promotes aberrant proliferation of Mes HGGs and GSCs.
Journal ArticleDOI

Aldehyde Dehydrogenase Inhibitors: a Comprehensive Review of the Pharmacology, Mechanism of Action, Substrate Specificity, and Clinical Application

TL;DR: The purpose of this review is to establish the current status of pharmacological inhibition of the ALDHs, provide a rationale for the continued development of ALDH isozyme-selective inhibitors, and identify the challenges and potential therapeutic rewards associated with the creation of such agents.
Journal ArticleDOI

Aldehyde dehydrogenase 1A1 in stem cells and cancer

TL;DR: The functions and mechanisms of ALDH1A1, the key ALDH isozyme linked to SC populations and an important contributor to CSC function in cancers, are reviewed, and its potential in future anticancer strategies is outlined.
Journal ArticleDOI

Evidence of β-Cell Dedifferentiation in Human Type 2 Diabetes

TL;DR: The data support the view that pancreatic β-cells become dedifferentiated and convert to α- and δ-"like" cells in human type 2 diabetes, and should prompt a reassessment of goals in the prevention and treatment of β-cell dysfunction.
Journal ArticleDOI

Lipid Desaturation Is a Metabolic Marker and Therapeutic Target of Ovarian Cancer Stem Cells

TL;DR: It is shown that increased lipid unsaturation is a metabolic marker for ovarian CSCs and a target for CSC-specific therapy and Mechanistically, it is demonstrated that nuclear factor κB (NF-κB) directly regulates the expression levels of lipid desaturases, and inhibition of desaturase blocks NF-κBs signaling.
References
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Journal ArticleDOI

Prospective identification of tumorigenic breast cancer cells

TL;DR: The ability to prospectively identify tumorigenic cancer cells will facilitate the elucidation of pathways that regulate their growth and survival and strategies designed to target this population may lead to more effective therapies.
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The basics of epithelial-mesenchymal transition

TL;DR: Processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias and the identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes.
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Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell

TL;DR: It is demonstrated that the cell capable of initiating human AML in non-obese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice) — termed the SCID leukemia-initiating cell, or SL-IC — possesses the differentiate and proliferative capacities and the potential for self-renewal expected of a leukemic stem cell.
Journal ArticleDOI

Glioma stem cells promote radioresistance by preferential activation of the DNA damage response

TL;DR: This work shows that cancer stem cells contribute to glioma radioresistance through preferential activation of the DNA damage checkpoint response and an increase in DNA repair capacity, and suggests that CD133-positive tumour cells could be the source of tumour recurrence after radiation.
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Multidrug resistance in cancer: role of ATP–dependent transporters

TL;DR: The ability to predict and circumvent drug resistance is likely to improve chemotherapy, and it has become apparent that resistance exists against every effective drug, even the authors' newest agents.
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