Project B7

Transcription Factor-Dependent Regulation of HCC Growth and Migration

Principal Investigator: PD Dr. Kai Breuhahn

Short Summary

The overexpression of far-upstream element (FUSE)-binding proteins (FBPs), transcription factors found in most human HCCs, supports proliferation and migration partly through microtubule-interacting proteins. However, the molecular mechanisms by which FBPs exert their pro-tumorigenic effects are currently unknown. In order to develop novel strategies targeting FBP activity, the molecular and functional dissection of FBP family members in HCC cells is necessary. Lastly, the therapeutic relevance of FBPs will be demonstrated in appropriate in vivo models after e.g. pharmacological inhibition of upstream regulators and downstream effectors.


List of relevant publications

  1. Singer S, Malz M, Herpel E, Warth A, Bissinger M, Keith M, Muley T, Meister M, Hoffmann H, Penzel R, Gdynia G, Ehemann V, Schnabel PA, Kuner R, Huber P, Schirmacher P, Breuhahn K (2009) Coordinated expression of stathmin family members by far upstream sequence element (FUSE)-binding protein (FBP)-1 increased motility in non-small cell lung cancer. Cancer Res 69:2234-43.
  2. Schnickmann S, Camacho-Trullio D, Bissinger M, Eils R, Angel P, Schirmacher P, Szabowski A, Breuhahn K (2009) AP-1-Controlled Hepatocyte Growth Factor Activation Promotes Keratinocyte Migration via CEACAM1 and Urokinase Plasminogen Activator/Urokinase Plasminogen Receptor. J Invest Dermatol (Nov 20, Epub ahead).
  3. Nussbaum T, Samarin J, Ehemann V, Bissinger M, Ryschich E, Khamidjanov A, Yu X, Gretz N, Schirmacher P, Breuhahn K (2008) Autocrine insulin-like growth factor-II stimulation of tumor cell migration is a progression step in human hepatocarcinogenesis. Hepatology 48:146-56.
  4. Busch H, Camacho-Trullio D, Rogon Z, Breuhahn K, Angel P, Eils R, Szabowski A (2008) Gene network dynamics controlling keratinocyte migration. Mol Syst Biol 4:199.
  5. Singer S, Ehemann V, Brauckhoff A, Keith M, Vreden S, Schirmacher P, Breuhahn K (2007) Protumorigenic overexpression of stathmin/Op18 by gain-of-function mutation in p53 in human hepatocarcinogenesis. Hepatology 46:759-68.
  6. Breuhahn K, Longerich T, Schirmacher P (2006) Dysregulation of growth factor signaling in human hepatocellular carcinoma. Oncogene 25:3787-800.
  7. Moinzadeh P*, Breuhahn K*, Stutzer H, Schirmacher P (2005) Chromosome alterations in human hepatocellular carcinomas correlate with aetiology and histological grade - results of an explorative CGH meta-analysis. Br J Cancer 92:935-41. (*shared first authorship)
  8. Breuhahn K, Vreden S, Haddad R, Beckebaum S, Stippel D, Flemming P, Nussbaum T, Caselmann WH, Haab BB, Schirmacher P (2004) Molecular profiling of human hepatocellular carcinoma defines mutually exclusive interferon regulation and insulin-like growth factor II overexpression. Cancer Res 64:6058-64.
  9. Kern MA, Breuhahn K, Schirmacher P (2002) Molecular pathogenesis of human hepatocellular carcinoma. Adv Cancer Res 86:67-112.
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