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

Chapter

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.

Keywords

Cancer stem cells DNA repair EMT Metastasis Pancreatic cancer RAD51 

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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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of SurgeryVanderbilt University School of MedicineNashvilleUSA
  2. 2.Department of Pathology & Laboratory MedicineMedical University of South CarolinaCharlestonUSA

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