Contribution of epithelial-mesenchymal transition to pancreatic cancer progression

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Abstract

Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies, with median survival of less than one year and overall five-year survival of less than 5%. There is increasing evidence demonstrating that epithelial-mesenchymal transition (EMT) contributes to pancreatic cancer metastasis and to treatment resistance. In this review, we will examine the data demonstrating the role and regulation of EMT in pancreatic cancer progression, focusing particularly on the transcription factors and microRNAs involved in EMT. We will examine how EMT is involved in the generation and maintenance of stem cells, and the role of EMT in modulating resistance of PDAC cells to drug therapies. We will also identify putative EMT-targeting agents that may help to reduce the morbidity and mortality associated with pancreatic cancer. © 2010 by the authors; licensee MDPI, Basel, Switzerland.

Figures

  • Figure 1. Schematic of epithelial to mesenchymal transition (EMT), including signaling pathways, transcription factors, and cell phenotype. Several cytokines and growth factors, notably TGF-β and TNF-α, along with the WNT, Notch, and Hedgehog pathways, induce EMT. The primary transcription factors in pancreatic cancer are Snail and Zeb1. Cell that undergo EMT lose their epithelial markers, such as E-cadherin and cytokeratin, and sheet like architecture and take on a mesenchymal phenotype with increased vimentin, fibronectin, and N-Cadherin expression along with single cell, spindle-like morphology. These cells can contribute to desmoplasia, are invasive, have stem-cell-like properties, and show increased chemoresistance.
  • Figure 2. Snail expression is associated with decreased E-Cadherin expression, increased vimentin, and a fibroblast-like phenotype. (A) Snail, E-cadherin, and vimentin mRNA expression as determined by qRT-PCR, normalized to GAPDH, in three pancreatic cancer cell lines, HPAF-II/CD18 (CD18), MiaPaCa-1 (MP1), and Panc1. (B) E-cadherin expression inversely correlates with vimentin expression in three pancreatic cancer cell lines as determined by Western blot. (C) Expression of Snail and E-cadherin, as determined by Western blot, in CD-18 pancreatic cancer cells induced to express either Snail or a control vector. (D) Growth architecture of CD-18 pancreatic cancer cells induced to express either Snail or a control vector.
  • Figure 3. Expression of the stem cell marker aldehyde dehydrogenase is associated with increased expression of Snail. Graph showing a comparison of aldehyde dehydrogenase (ALDH) expression, as measured by qRT-PCR, normalized to GAPDH, in CD-18 pancreatic cancer cells induced to express either Snail or a control vector.

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CITATION STYLE

APA

Krantz, S. B., Shields, M. A., Dangi-Garimella, S., Bentrem, D. J., & Munshi, H. G. (2010, December). Contribution of epithelial-mesenchymal transition to pancreatic cancer progression. Cancers. https://doi.org/10.3390/cancers2042084

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