@article{MoenchGrimmigKannenetal.2016,
  author    = {Moench, Romana and Grimmig, Tanja and Kannen, Vinicius and Tripathi, Sudipta and Faber, Marc and Moll, Eva-Maria and Chandraker, Anil and Lissner, Reinhard and Germer, Christoph-Thomas and Waaga-Gasser, Ana Maria and Gasser, Martin},
  title     = {Exclusive inhibition of PI3K/Akt/mTOR signaling is not sufficient to prevent PDGF-mediated effects on glycolysis and proliferation in colorectal cancer},
  series = {Oncotarget},
  volume    = {7},
  journal   = {Oncotarget},
  number    = {42},
  doi       = {10.18632/oncotarget.11899},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176910},
  pages     = {68749-68767},
  year      = {2016},
  abstract  = {Platelet-derived growth factor (PDGF) and signaling via its receptors plays a crucial role in tumor cell proliferation and thus may represent an attractive target besides VEGF/EGFR-based antibody therapies. In this study we analyzed the influence of PDGF in colorectal cancer. PDGF was expressed intensively in early and even more intensively in late stage primary CRCs. Like VEGF, PDGF enhanced human colon cancer proliferation, and increased oxidative glycolytic activity, and activated HIF1α and c-Myc in vitro. PDGF activated the PI3K/Akt/mTOR pathway while leaving MAPK signaling untouched. Further dissection showed that inhibition of Akt strongly impeded cancer cell growth while inhibition of PI3K did not. MAPK analysis suggested an inhibitory crosstalk between both pathways, thus explaining the different effects of the Akt and PI3K inhibitors on cancer cell proliferation. PDGF stimulates colon cancer cell proliferation, and prevents inhibitor induced apoptosis, resulting in tumor growth. Therefore inhibition of PDGF signaling seems to be a promising target in colorectal cancer therapy. However, due to the multifaceted nature of the intracellular PDGF signaling, careful intervention strategies are needed when looking into specific signaling pathways like PI3K/Akt/mTOR and MAPK.},
  language  = {en}
}
@article{GrimmigMoenchKreckeletal.2016,
  author    = {Grimmig, Tanja and Moench, Romana and Kreckel, Jennifer and Haack, Stephanie and Rueckert, Felix and Rehder, Roberta and Tripathi, Sudipta and Ribas, Carmen and Chandraker, Anil and Germer, Christoph T. and Gasser, Martin and Waaga-Gasser, Ana Maria},
  title     = {Toll Like Receptor 2, 4, and 9 Signaling Promotes Autoregulative Tumor Cell Growth and VEGF/PDGF Expression in Human Pancreatic Cancer},
  series = {International Journal of Molecular Sciences},
  volume    = {17},
  journal   = {International Journal of Molecular Sciences},
  number    = {12},
  doi       = {10.3390/ijms17122060},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165743},
  pages     = {2060},
  year      = {2016},
  abstract  = {Toll like receptor (TLR) signaling has been suggested to play an important role in the inflammatory microenvironment of solid tumors and through this inflammation-mediated tumor growth. Here, we studied the role of tumor cells in their process of self-maintaining TLR expression independent of inflammatory cells and cytokine milieu for autoregulative tumor growth signaling in pancreatic cancer. We analyzed the expression of TLR2, -4, and -9 in primary human cancers and their impact on tumor growth via induced activation in several established pancreatic cancers. TLR-stimulated pancreatic cancer cells were specifically investigated for activated signaling pathways of VEGF/PDGF and anti-apoptotic Bcl-xL expression as well as tumor cell growth. The primary pancreatic cancers and cell lines expressed TLR2, -4, and -9. TLR-specific stimulation resulted in activated MAP-kinase signaling, most likely via autoregulative stimulation of demonstrated TLR-induced VEGF and PDGF expression. Moreover, TLR activation prompted the expression of Bcl-xL and has been demonstrated for the first time to induce tumor cell proliferation in pancreatic cancer. These findings strongly suggest that pancreatic cancer cells use specific Toll like receptor signaling to promote tumor cell proliferation and emphasize the particular role of TLR2, -4, and -9 in this autoregulative process of tumor cell activation and proliferation in pancreatic cancer.},
  language  = {en}
}