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DNA Repair of Cancer Stem Cells pp 141–155Cite as

Pancreatic Cancer Stem Cells in Tumor Progression, Metastasis, Epithelial-Mesenchymal Transition and DNA Repair

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Abstract

Pancreatic cancer is an aggressive solid malignancy with poor response to therapy and the subsequent dismal survival rate has remained a hallmark of this disease. There is evidence to indicate that pancreatic cancer is initiated and propagated by cancer stem cell (CSC)s. The CSC population is defined by its tumor initiating capacity and has been shown to be invasive or metastatic. Loss of genome stability is a hallmark of cancer with DNA repair enzymes aiding in maintenance of stability. The potential to assess the risk of cancer development lies in careful determination of one’s capacity in nurturing genome stability. DNA repair genes are over expressed in CSCs and both pancreatic CSCs and invasive cells in turn provide greater DNA damage response and repair mechanisms. Pancreatic tumor-initiating cells as well as invasive cells have a large number of genes related to DNA repair. RAD51, the key player in the recombinational repair of damaged DNA might act as a critical mediator of efficient DNA repair mechanisms of CSCs. We update here the current research results regarding CSCs in pancreatic cancer progression, metastasis and discuss the DNA repair mechanism in pancreatic CSCs.

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Abbreviations

ALDH:

Aldehyde dehydrogenase

BER:

Base excision repair

CSCs:

Cancer stem cells

CXCR4:

CXC chemokine receptor 4

DSB:

Double-strand break

EMT:

Epithelial to mesenchymal transition

EpCAM:

Epithelial cell adhesion molecule

ESA:

Epithelial specific antigen

HMG CoA:

3-hydroxy-3-methylglutaryl coenzyme A reductase

HR:

Homologous recombination

MMR:

Mismatch repair

NER:

Nucleotide excision repair

NHEJ:

Non-homologous end-joining

PARP:

Poly ADP ribose polymerase

PDAC:

Pancreatic ductal adenocarcinoma

SCs:

Stem cells

SDF-1:

Stromal derived factor-1

SSB:

Single-strand break

TGF-β:

Transforming growth factor beta

ZEB:

Zinc-finger transcription factor

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Acknowledgments

We thank Drs. Nipun Merchant, Elaine Hurt, Stephanie Cabarcas, Lesley Mathews and Michael Van Saun for their useful comments and stimulating discussions during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Surgery, Vanderbilt University School of Medicine, 1161, 21st Ave S., D2300 MCN, 37232, Nashville, TN, USA

    Nagaraj S. Nagathihalli

  2. Department of Pathology & Laboratory Medicine, Medical University of South Carolina, 29425, Charleston, SC, USA

    Erika T. Brown

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  1. Nagaraj S. Nagathihalli
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  2. Erika T. Brown
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Corresponding author

Correspondence to Nagaraj S. Nagathihalli .

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Editors and Affiliations

  1. Division of Pre-Clinical Innovation, Nat. Center for Advancing Transl. Scie, National Institutes of Health, BLDG B, RM 1004 9800, Rockville, 20850, Maryland, USA

    Lesley A Mathews

  2. Gannon University, University Square 109, Erie, 16541, Pennsylvania, USA

    Stephanie M Cabarcas

  3. Preclinical Oncology Research, MedImmune Way 1, Gaithersburg, 20878, Maryland, USA

    Elaine M. Hurt

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Nagathihalli, N., Brown, E. (2013). Pancreatic Cancer Stem Cells in Tumor Progression, Metastasis, Epithelial-Mesenchymal Transition and DNA Repair. In: Mathews, L., Cabarcas, S., Hurt, E. (eds) DNA Repair of Cancer Stem Cells. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4590-2_8

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