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Editorial
. 2013 Apr 15;12(8):1153-4.
doi: 10.4161/cc.24488. Epub 2013 Apr 2.

Induction of TRIF- or MYD88-dependent pathways perturbs cell cycle regulation in pancreatic cancer

Constantinos P Zambirinis, Atsuo Ochi, Rocky Barilla, Stephanie Greco, Michael Deutsch, George Miller
Editorial

Induction of TRIF- or MYD88-dependent pathways perturbs cell cycle regulation in pancreatic cancer

Constantinos P Zambirinis et al. Cell Cycle. .
No abstract available

Keywords: p16; p21; p27; p53; pancreatic cancer.

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Figures

None
Figure 1. Central role of Toll-like receptors in the tumor-microenvironment of pancreatic cancer. Kras-mutant epithelial cells attract immune cells, which, in turn, promote inflammation and cause stress and damage to pre-malignant epithelial cells. We postulate that epithelial cells may respond to stress by undergoing the process of oncogene-induced senescence (OIS), leading to upregulation of tumor-suppressor proteins such as p21, p27, p53 and pRB. Some of these cells will bypass the barrier of OIS and transform, whereas others will die and release DAMPs. DAMPs, in turn, can bind TLRs on immune cells, leading to worsening inflammation and completing a vicious circle. At the same time, inflammatory mediators such as IL-6 can directly signal to transformed cells and activate pathways such as STAT3 that promote an aggressive cancer phenotype featuring increased expression of oncoproteins such as c-Myc and Bcl-xL. Furthermore, cancer-associated fibroblasts can be activated by released DAMPs either directly or indirectly through the immune cells, causing intense fibrosis and further perpetuating inflammation. Toll-like receptors act as the sensors of the DAMPs and therefore participate in several of the above steps.
See this image and copyright information in PMC

Comment on

  • Ochi A, Graffeo CS, Zambirinis CP, Rehman A, Hackman M, Fallon N, et al. Toll-like receptor 7 regulates pancreatic carcinogenesis in mice and humans. J Clin Invest. 2012;122:4118–29. doi: 10.1172/JCI63606. doi: 10.1172/JCI63606
  • Ochi A, Nguyen AH, Bedrosian AS, Mushlin HM, Zarbakhsh S, Barilla R, et al. MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells. J Exp Med. 2012;209:1671–87. doi: 10.1084/jem.20111706. doi: 10.1084/jem.20111706

References

    1. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010;140:805–20. doi: 10.1016/j.cell.2010.01.022. - DOI - PubMed
    1. Rakoff-Nahoum S, Medzhitov R. Toll-like receptors and cancer. Nat Rev Cancer. 2009;9:57–63. doi: 10.1038/nrc2541. - DOI - PubMed
    1. Ochi A, Graffeo CS, Zambirinis CP, Rehman A, Hackman M, Fallon N, et al. Toll-like receptor 7 regulates pancreatic carcinogenesis in mice and humans. J Clin Invest. 2012;122:4118–29. doi: 10.1172/JCI63606. - DOI - PMC - PubMed
    1. Ochi A, Nguyen AH, Bedrosian AS, Mushlin HM, Zarbakhsh S, Barilla R, et al. MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells. J Exp Med. 2012;209:1671–87. doi: 10.1084/jem.20111706. - DOI - PMC - PubMed
    1. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009;9:798–809. doi: 10.1038/nrc2734. - DOI - PMC - PubMed

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